Biochemistry, Genetics and Molecular Biology › Cancer Research

Cancer-related molecular mechanisms research

Works Count: 109765

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This cluster of papers explores the role of long noncoding RNAs (lncRNAs) in cancer, development, and genome regulation. It covers topics such as the transcriptional landscape, epigenetic regulation, chromatin modification, competing endogenous RNA networks, and the impact of lncRNAs on cell differentiation. The papers also delve into the functional classification and molecular mechanisms of lncRNAs, highlighting their significance in human diseases.

Keywords

Long Noncoding RNAs; Cancer; RNA Regulation; Epigenetic Regulation; Transcriptional Landscape; Cell Differentiation; Chromatin Modification; Competing Endogenous RNA; Genome Regulation; Non-coding RNA Networks

Long Noncoding RNAs: Cellular Address Codes in Development and Disease

2013-03-01

Pedro J. Batista , Howard Y. Chang

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Modular regulatory principles of large non-coding RNAs

2012-02-01

Mitchell Guttman , John L. Rinn

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The hallmarks of cancer

2012-06-01

Tony Gutschner , Sven Diederichs

With the advent of next generation sequencing methods and progress in transcriptome analysis, it became obvious that the human genome contains much more than just protein-coding genes. In fact, up … With the advent of next generation sequencing methods and progress in transcriptome analysis, it became obvious that the human genome contains much more than just protein-coding genes. In fact, up to 70% of our genome is transcribed into RNA that does not serve as templates for proteins. In this review, we focus on the emerging roles of these long non-coding RNAs (lncRNAs) in the field of tumor biology. Long ncRNAs were found to be deregulated in several human cancers and show tissue-specific expression. Functional studies revealed a broad spectrum of mechanisms applied by lncRNAs such as HOTAIR, MALAT1, ANRIL or lincRNA-p21 to fulfill their functions. Here, we link the cellular processes influenced by long ncRNAs to the hallmarks of cancer and therefore provide an ncRNA point-of-view on tumor biology. This should stimulate new research directions and therapeutic options considering long ncRNAs as novel prognostic markers and therapeutic targets.

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Long noncoding RNAs: functional surprises from the RNA world

2009-07-01

Jeremy E. Wilusz , Hongjae Sunwoo , David L. Spector

Most of the eukaryotic genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs with little or no protein-coding capacity. Although the … Most of the eukaryotic genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs with little or no protein-coding capacity. Although the vast majority of long noncoding RNAs have yet to be characterized thoroughly, many of these transcripts are unlikely to represent transcriptional “noise” as a significant number have been shown to exhibit cell type-specific expression, localization to subcellular compartments, and association with human diseases. Here, we highlight recent efforts that have identified a myriad of molecular functions for long noncoding RNAs. In some cases, it appears that simply the act of noncoding RNA transcription is sufficient to positively or negatively affect the expression of nearby genes. However, in many cases, the long noncoding RNAs themselves serve key regulatory roles that were assumed previously to be reserved for proteins, such as regulating the activity or localization of proteins and serving as organizational frameworks of subcellular structures. In addition, many long noncoding RNAs are processed to yield small RNAs or, conversely, modulate how other RNAs are processed. It is thus becoming increasingly clear that long noncoding RNAs can function via numerous paradigms and are key regulatory molecules in the cell.

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Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals

2009-02-01

Mitchell Guttman , Ido Amit , Manuel Garber +7 more

Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells

2013-08-09

Liying Yan , Ming‐Yu Yang , Hongshan Guo +7 more

The landscape of long noncoding RNAs in the human transcriptome

2015-01-19

Matthew K. Iyer , Yashar S. Niknafs , Rohit Malik +7 more

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Long non-coding RNAs: new players in cell differentiation and development

2013-12-03

Alessandro Fatica , Irene Bozzoni

Long noncoding RNAs and human disease

2011-05-10

Orly L. Wapinski , Howard Y. Chang

A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?

2011-08-01

Leonardo Salmena , Laura Poliseno , Yvonne Tay +2 more

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CPAT: Coding-Potential Assessment Tool using an alignment-free logistic regression model

2013-01-17

Liguo Wang , Hyun Jung Park , Surendra Dasari +3 more

Thousands of novel transcripts have been identified using deep transcriptome sequencing. This discovery of large and 'hidden' transcriptome rejuvenates the demand for methods that can rapidly distinguish between coding and … Thousands of novel transcripts have been identified using deep transcriptome sequencing. This discovery of large and 'hidden' transcriptome rejuvenates the demand for methods that can rapidly distinguish between coding and noncoding RNA. Here, we present a novel alignment-free method, Coding Potential Assessment Tool (CPAT), which rapidly recognizes coding and noncoding transcripts from a large pool of candidates. To this end, CPAT uses a logistic regression model built with four sequence features: open reading frame size, open reading frame coverage, Fickett TESTCODE statistic and hexamer usage bias. CPAT software outperformed (sensitivity: 0.96, specificity: 0.97) other state-of-the-art alignment-based software such as Coding-Potential Calculator (sensitivity: 0.99, specificity: 0.74) and Phylo Codon Substitution Frequencies (sensitivity: 0.90, specificity: 0.63). In addition to high accuracy, CPAT is approximately four orders of magnitude faster than Coding-Potential Calculator and Phylo Codon Substitution Frequencies, enabling its users to process thousands of transcripts within seconds. The software accepts input sequences in either FASTA- or BED-formatted data files. We also developed a web interface for CPAT that allows users to submit sequences and receive the prediction results almost instantly.

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A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression

2011-03-20

Ke Wang , Yul W. Yang , Бо Лю +7 more

Circular Intronic Long Noncoding RNAs

2013-09-01

Yang Zhang , Xiao‐Ou Zhang , Chen Tian +6 more

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Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts

2013-07-27

Liang Sun , Haitao Luo , Dechao Bu +6 more

It is a challenge to classify protein-coding or non-coding transcripts, especially those re-constructed from high-throughput sequencing data of poorly annotated species. This study developed and evaluated a powerful signature tool, … It is a challenge to classify protein-coding or non-coding transcripts, especially those re-constructed from high-throughput sequencing data of poorly annotated species. This study developed and evaluated a powerful signature tool, Coding-Non-Coding Index (CNCI), by profiling adjoining nucleotide triplets to effectively distinguish protein-coding and non-coding sequences independent of known annotations. CNCI is effective for classifying incomplete transcripts and sense-antisense pairs. The implementation of CNCI offered highly accurate classification of transcripts assembled from whole-transcriptome sequencing data in a cross-species manner, that demonstrated gene evolutionary divergence between vertebrates, and invertebrates, or between plants, and provided a long non-coding RNA catalog of orangutan. CNCI software is available at http://www.bioinfo.org/software/cnci.

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Molecular Mechanisms of Long Noncoding RNAs

2011-09-01

Ke Wang , Howard Y. Chang

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Long non-coding RNAs: insights into functions

2009-02-03

Tim R. Mercer , Marcel E. Dinger , John S. Mattick

Evolution and Functions of Long Noncoding RNAs

2009-02-01

Chris P. Ponting , Peter L. Oliver , Wolf Reik

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GENCODE: The reference human genome annotation for The ENCODE Project

2012-09-01

Jennifer Harrow , Adam Frankish , José M. González +7 more

The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of … The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.

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Genome Regulation by Long Noncoding RNAs

2012-06-05

John L. Rinn , Howard Y. Chang

The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. The discovery of extensive transcription of … The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long noncoding RNAs (lncRNAs), provides an important new perspective on the centrality of RNA in gene regulation. Here, we discuss genome-scale strategies to discover and characterize lncRNAs. An emerging theme from multiple model systems is that lncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators and then target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, lncRNAs can function as modular scaffolds to specify higher-order organization in RNP complexes and in chromatin states. The importance of these modes of regulation is underscored by the newly recognized roles of long RNAs for proper gene control across all kingdoms of life.

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A scaling normalization method for differential expression analysis of RNA-seq data

2010-03-02

Mark D. Robinson , Alicia Oshlack

Abstract The fine detail provided by sequencing-based transcriptome surveys suggests that RNA-seq is likely to become the platform of choice for interrogating steady state RNA. In order to discover biologically … Abstract The fine detail provided by sequencing-based transcriptome surveys suggests that RNA-seq is likely to become the platform of choice for interrogating steady state RNA. In order to discover biologically important changes in expression, we show that normalization continues to be an essential step in the analysis. We outline a simple and effective method for performing normalization and show dramatically improved results for inferring differential expression in simulated and publicly available data sets.

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The Emergence of lncRNAs in Cancer Biology

2011-10-01

John R. Prensner , Arul M. Chinnaiyan

The discovery of numerous noncoding RNA (ncRNA) transcripts in species from yeast to mammals has dramatically altered our understanding of cell biology, especially the biology of diseases such as cancer. … The discovery of numerous noncoding RNA (ncRNA) transcripts in species from yeast to mammals has dramatically altered our understanding of cell biology, especially the biology of diseases such as cancer. In humans, the identification of abundant long ncRNA (lncRNA) >200 bp has catalyzed their characterization as critical components of cancer biology. Recently, roles for lncRNAs as drivers of tumor suppressive and oncogenic functions have appeared in prevalent cancer types, such as breast and prostate cancer. In this review, we highlight the emerging impact of ncRNAs in cancer research, with a particular focus on the mechanisms and functions of lncRNAs.

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MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review

2012-02-20

Marilena V. Iorio , Carlo M. Croce

Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs

2007-06-01

John L. Rinn , Michael A. Kertesz , Jordon K. Wang +7 more

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starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data

2013-12-01

Jun-Hao Li , Shun Liu , Hui Zhou +2 more

Although microRNAs (miRNAs), other non-coding RNAs (ncRNAs) (e.g.lncRNAs, pseudogenes and circRNAs) and competing endogenous RNAs (ceRNAs) have been implicated in cell-fate determination and in various human diseases, surprisingly little is … Although microRNAs (miRNAs), other non-coding RNAs (ncRNAs) (e.g.lncRNAs, pseudogenes and circRNAs) and competing endogenous RNAs (ceRNAs) have been implicated in cell-fate determination and in various human diseases, surprisingly little is known about the regulatory interaction networks among the multiple classes of RNAs.In this study, we developed starBase v2.0 (http://starbase.sysu.edu.cn/) to systematically identify the RNA-RNA and protein-RNA interaction networks from 108 CLIP-Seq (PAR-CLIP, HITS-CLIP, iCLIP, CLASH) data sets generated by 37 independent studies.By analyzing millions of RNA-binding protein binding sites, we identified $9000 miRNA-circRNA, 16 000 miRNApseudogene and 285 000 protein-RNA regulatory relationships.Moreover, starBase v2.0 has been updated to provide the most comprehensive CLIP-Seq experimentally supported miRNA-mRNA and miRNA-lncRNA interaction networks to date.We identified $10 000 ceRNA pairs from CLIP-supported miRNA target sites.By combining 13 functional genomic annotations, we developed miRFunction and ceRNAFunction web servers to predict the function of miRNAs and other ncRNAs from the miRNAmediated regulatory networks.Finally, we developed interactive web implementations to provide visualization, analysis and downloading of the aforementioned large-scale data sets.This study will greatly expand our understanding of ncRNA functions and their coordinated regulatory networks.

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Integrated genomic analyses of ovarian carcinoma

2011-06-28

Debra Bell , Andrew Berchuck , Michael J. Birrer +7 more

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Non-coding RNA

2006-04-15

John S. Mattick , Igor V. Makunin

The term non-coding RNA (ncRNA) is commonly employed for RNA that does not encode a protein, but this does not mean that such RNAs do not contain information nor have … The term non-coding RNA (ncRNA) is commonly employed for RNA that does not encode a protein, but this does not mean that such RNAs do not contain information nor have function. Although it has been generally assumed that most genetic information is transacted by proteins, recent evidence suggests that the majority of the genomes of mammals and other complex organisms is in fact transcribed into ncRNAs, many of which are alternatively spliced and/or processed into smaller products. These ncRNAs include microRNAs and snoRNAs (many if not most of which remain to be identified), as well as likely other classes of yet-to-be-discovered small regulatory RNAs, and tens of thousands of longer transcripts (including complex patterns of interlacing and overlapping sense and antisense transcripts), most of whose functions are unknown. These RNAs (including those derived from introns) appear to comprise a hidden layer of internal signals that control various levels of gene expression in physiology and development, including chromatin architecture/epigenetic memory, transcription, RNA splicing, editing, translation and turnover. RNA regulatory networks may determine most of our complex characteristics, play a significant role in disease and constitute an unexplored world of genetic variation both within and between species.

Non-coding RNAs and cancer: microRNAs and beyond

2011-03-11

Rachel Marie Raia , George A. Călin

MicroRNAs (miRNAs) are small RNAs that regulate the expression of complementary messenger RNAs. Hundreds of miRNA genes have been found in diverse animals, and many of these are phylogenetically conserved. … MicroRNAs (miRNAs) are small RNAs that regulate the expression of complementary messenger RNAs. Hundreds of miRNA genes have been found in diverse animals, and many of these are phylogenetically conserved. With miRNA roles identified in developmental timing, cell death, cell proliferation, haematopoiesis and patterning of the nervous system, evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.

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Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes

2010-07-09

Miao-Chih Tsai , Ohad Manor , Yue Wan +6 more

A Lot of HOTAIR The roles of several classes of small (<50 nucleotides) noncoding RNAs are beginning to be defined in molecular detail, whereas the function of most of the … A Lot of HOTAIR The roles of several classes of small (<50 nucleotides) noncoding RNAs are beginning to be defined in molecular detail, whereas the function of most of the long (∼200+ nucleotides), intergenic noncoding (linc)RNAs found in most eukaryotic genomes remains something of a mystery. The HOTAIR lincRNA, which is transcribed from the mouse HOXC locus, binds to the Polycomb Repressive Complex 2 (PRC2) and recruits it to HOXD and other genes, where its histone methylase activity acts to repress gene transcription. Tsai et al. (p. 689 , published online 8 July) now show that HOTAIR also binds to a histone demethylase enzyme, LSD1, part of the CoREST/REST repressor complex. LSD1 acts to remove transcription-activating histone marks, reinforcing the repressive activity of the PRC2 complex. HOTAIR thus functions as a platform for the coordinated binding of PRC2 and LSD1-containing complexes to genes, as revealed in a genome-wide analysis of PRC1/CoREST/REST co-regulated genes.

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Long Noncoding RNAs: Past, Present, and Future

2013-03-01

Johnny T. Kung , David Colognori , Jeannie T. Lee

Abstract Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in … Abstract Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology’s longstanding concern with the evolution and function of genomes.

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The multilayered complexity of ceRNA crosstalk and competition

2014-01-01

Yvonne Tay , John L. Rinn , Pier Paolo Pandolfi

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Long Noncoding RNAs with Enhancer-like Function in Human Cells

2010-10-01

Ulf Andersson Ørom , Thomas Derrien , Malte Beringer +7 more

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voom: precision weights unlock linear model analysis tools for RNA-seq read counts

2014-02-03

Charity W. Law , Yunshun Chen , Wei Shi +1 more

Abstract New normal linear modeling strategies are presented for analyzing read counts from RNA-seq experiments. The voom method estimates the mean-variance relationship of the log-counts, generates a precision weight for … Abstract New normal linear modeling strategies are presented for analyzing read counts from RNA-seq experiments. The voom method estimates the mean-variance relationship of the log-counts, generates a precision weight for each observation and enters these into the limma empirical Bayes analysis pipeline. This opens access for RNA-seq analysts to a large body of methodology developed for microarrays. Simulation studies show that voom performs as well or better than count-based RNA-seq methods even when the data are generated according to the assumptions of the earlier methods. Two case studies illustrate the use of linear modeling and gene set testing methods.

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A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

2010-08-01

Maite Huarte , Mitchell Guttman , David M. Feldser +7 more

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The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression

2012-09-01

Thomas Derrien , Rory Johnson , Giovanni Bussotti +7 more

The human genome contains many thousands of long noncoding RNAs (lncRNAs). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate … The human genome contains many thousands of long noncoding RNAs (lncRNAs). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate these genes have been hampered by the lack of comprehensive lncRNA annotation. Here, we present and analyze the most complete human lncRNA annotation to date, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts. Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths. In contrast to protein-coding genes, however, lncRNAs display a striking bias toward two-exon transcripts, they are predominantly localized in the chromatin and nucleus, and a fraction appear to be preferentially processed into small RNAs. They are under stronger selective pressure than neutrally evolving sequences—particularly in their promoter regions, which display levels of selection comparable to protein-coding genes. Importantly, about one-third seem to have arisen within the primate lineage. Comprehensive analysis of their expression in multiple human organs and brain regions shows that lncRNAs are generally lower expressed than protein-coding genes, and display more tissue-specific expression patterns, with a large fraction of tissue-specific lncRNAs expressed in the brain. Expression correlation analysis indicates that lncRNAs show particularly striking positive correlation with the expression of antisense coding genes. This GENCODE annotation represents a valuable resource for future studies of lncRNAs.

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Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression

2009-07-02

Ahmad M. Khalil , Mitchell Guttman , Maite Huarte +7 more

We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc)RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in … We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc)RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes, including cell-cycle regulation, immune surveillance, and embryonic stem cell pluripotency. However, the mechanism by which these lincRNAs function is unknown. Here, we expand the catalog of human lincRNAs to ≈3,300 by analyzing chromatin-state maps of various human cell types. Inspired by the observation that the well-characterized lincRNA HOTAIR binds the polycomb repressive complex (PRC)2, we tested whether many lincRNAs are physically associated with PRC2. Remarkably, we observe that ≈20% of lincRNAs expressed in various cell types are bound by PRC2, and that additional lincRNAs are bound by other chromatin-modifying complexes. Also, we show that siRNA-mediated depletion of certain lincRNAs associated with PRC2 leads to changes in gene expression, and that the up-regulated genes are enriched for those normally silenced by PRC2. We propose a model in which some lincRNAs guide chromatin-modifying complexes to specific genomic loci to regulate gene expression.

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A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA

2011-10-01

Marcella Cesana , Davide Cacchiarelli , Ivano Legnini +5 more

Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis

2010-04-01

Rajnish A. Gupta , Nilay Shah , Ke Wang +7 more

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lincRNAs act in the circuitry controlling pluripotency and differentiation

2011-08-26

Mitchell Guttman , Julie Donaghey , Bryce W. Carey +7 more

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lincRNAs: Genomics, Evolution, and Mechanisms

2013-07-01

Igor Ulitsky , David P. Bartel

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Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses

2011-09-02

Moran N. Cabili , Cole Trapnell , Loyal A. Goff +4 more

Large intergenic noncoding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes. Determining the function of individual lincRNAs remains a challenge. Recent advances in RNA sequencing (RNA-seq) and … Large intergenic noncoding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes. Determining the function of individual lincRNAs remains a challenge. Recent advances in RNA sequencing (RNA-seq) and computational methods allow for an unprecedented analysis of such transcripts. Here, we present an integrative approach to define a reference catalog of >8000 human lincRNAs. Our catalog unifies previously existing annotation sources with transcripts we assembled from RNA-seq data collected from ∼4 billion RNA-seq reads across 24 tissues and cell types. We characterize each lincRNA by a panorama of >30 properties, including sequence, structural, transcriptional, and orthology features. We found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that lincRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes. We distinguish an additional subset of transcripts that have high evolutionary conservation but may include short ORFs and may serve as either lincRNAs or small peptides. Our integrated, comprehensive, yet conservative reference catalog of human lincRNAs reveals the global properties of lincRNAs and will facilitate experimental studies and further functional classification of these genes.

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The emerging role of lncRNAs in cancer

2015-11-01

Maite Huarte

Chronic Inflammation and Cytokines in the Tumor Microenvironment

2014-01-01

Glauben Landskron , Marjorie De la Fuente , Peti Thuwajit +2 more

Acute inflammation is a response to an alteration induced by a pathogen or a physical or chemical insult, which functions to eliminate the source of the damage and restore homeostasis … Acute inflammation is a response to an alteration induced by a pathogen or a physical or chemical insult, which functions to eliminate the source of the damage and restore homeostasis to the affected tissue. However, chronic inflammation triggers cellular events that can promote malignant transformation of cells and carcinogenesis. Several inflammatory mediators, such as TNF- α , IL-6, TGF- β , and IL-10, have been shown to participate in both the initiation and progression of cancer. In this review, we explore the role of these cytokines in important events of carcinogenesis, such as their capacity to generate reactive oxygen and nitrogen species, their potential mutagenic effect, and their involvement in mechanisms for epithelial mesenchymal transition, angiogenesis, and metastasis. Finally, we will provide an in-depth analysis of the participation of these cytokines in two types of cancer attributable to chronic inflammatory disease: colitis-associated colorectal cancer and cholangiocarcinoma.

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Differential analysis of gene regulation at transcript resolution with RNA-seq

2012-12-09

Cole Trapnell , David G. Hendrickson , Martin Sauvageau +3 more

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Unique features of long non-coding RNA biogenesis and function

2015-12-15

Jeffrey J. Quinn , Howard Y. Chang

Long Noncoding RNAs in Cancer Pathways

2016-04-01

Adam M. Schmitt , Howard Y. Chang

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Endogenous microRNA sponges: evidence and controversy

2016-04-04

Daniel Thomson , Marcel E. Dinger

Long Noncoding RNA and Cancer: A New Paradigm

2017-07-13

Arunoday Bhan , Milad Soleimani , Subhrangsu S. Mandal

Abstract In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in … Abstract In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in cancer. Genome-wide association studies of tumor samples have identified a large number of lncRNAs associated with various types of cancer. Alterations in lncRNA expression and their mutations promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and -promoting (oncogenic) functions. Because of their genome-wide expression patterns in a variety of tissues and their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. In this article, we have reviewed the emerging functions and association of lncRNAs in different types of cancer and discussed their potential implications in cancer diagnosis and therapy. Cancer Res; 77(15); 3965–81. ©2017 AACR.

Functional Classification and Experimental Dissection of Long Noncoding RNAs

2018-01-01

Florian Kopp , Joshua T. Mendell

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miRBase: from microRNA sequences to function

2018-10-25

Ana Kozomara , Maria Birgaoanu , Sam Griffiths‐Jones

miRBase catalogs, names and distributes microRNA gene sequences. The latest release of miRBase (v22) contains microRNA sequences from 271 organisms: 38 589 hairpin precursors and 48 860 mature microRNAs. We … miRBase catalogs, names and distributes microRNA gene sequences. The latest release of miRBase (v22) contains microRNA sequences from 271 organisms: 38 589 hairpin precursors and 48 860 mature microRNAs. We describe improvements to the database and website to provide more information about the quality of microRNA gene annotations, and the cellular functions of their products. We have collected 1493 small RNA deep sequencing datasets and mapped a total of 5.5 billion reads to microRNA sequences. The read mapping patterns provide strong support for the validity of between 20% and 65% of microRNA annotations in different well-studied animal genomes, and evidence for the removal of >200 sequences from the database. To improve the availability of microRNA functional information, we are disseminating Gene Ontology terms annotated against miRBase sequences. We have also used a text-mining approach to search for microRNA gene names in the full-text of open access articles. Over 500 000 sentences from 18 542 papers contain microRNA names. We score these sentences for functional information and link them with 12 519 microRNA entries. The sentences themselves, and word clouds built from them, provide effective summaries of the functional information about specific microRNAs. miRBase is publicly and freely available at http://mirbase.org/.

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Gene regulation by long non-coding RNAs and its biological functions

2020-12-22

Luisa Statello , Chunjie Guo , Ling‐Ling Chen +1 more

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Single-cell transcriptome and multi-omics integration reveal ferroptosis-driven immune microenvironment remodeling in knee osteoarthritis

2025-06-25

Yuan Wu , Jing Liu , Wen-Ying Yu +3 more | Frontiers in Immunology

Background Knee osteoarthritis (KOA) is a chronic inflammatory joint disorder marked by cartilage degradation and immune microenvironment dysregulation. While transcriptomic studies have identified key pathways in KOA, the interplay between … Background Knee osteoarthritis (KOA) is a chronic inflammatory joint disorder marked by cartilage degradation and immune microenvironment dysregulation. While transcriptomic studies have identified key pathways in KOA, the interplay between ferroptosis (an iron-dependent cell death mechanism) and immune dysfunction at single-cell resolution remains unexplored. This study integrates single-cell and bulk transcriptomics to dissect ferroptosis-driven immune remodeling and identify diagnostic biomarkers in KOA. Methods We analyzed scRNA-seq data (GSE255460, n = 11) and bulk RNA-seq cohorts (GSE114007: 20 KOA/18 controls; GSE246425: 8 KOA/4 controls). Single-cell data were processed via Seurat (QC: mitochondrial genes &gt;3 MAD; normalization: LogNormalize; batch correction: Harmony) and annotated using CellMarker/PanglaoDB. CellChat decoded intercellular communication, SCENIC reconstructed transcriptional networks, and Monocle2 for pseudotime trajectory mapping. Immune infiltration (CIBERSORT) and a LASSO-SVM diagnostic model were validated by ROC curves. Functional enrichment (GSEA/GSVA) and immunometabolic profiling were performed. Results Twelve chondrocyte clusters were identified, including ferroptosis-active homeostasis chondrocytes (HomC) ( p &lt; 0.01), which exhibited 491 DEGs linked to lipid peroxidation. HomC orchestrated synovitis via FGF signaling (ligand-receptor pairs: FGF1-FGFR1), amplifying ECM degradation and inflammatory cascades (CellChat). SCENIC revealed 10 HomC-specific regulons (e.g., SREBF1 , YY1 ) driving matrix metalloproteinase activation. A 7-gene diagnostic panel ( IFT88 , MIEF2 , ABCC10 , etc.) achieved AUC = 1.0 (training) and 0.78 (validation). Immune profiling showed reduced resting mast cells ( p = 0.003) and monocytes ( p = 0.02), with ABCC10 correlating negatively with CD8+ T cells ( r = -0.65) and M1 macrophages. GSEA/GSVA implicated HIF-1, NF-κB, and oxidative phosphorylation pathways in KOA progression. Pseudotime analysis revealed fibrotic transitions ( COL1A1 ↑, TNC ↑) in late-stage KOA cells. Conclusion This study establishes ferroptosis as one of the key drivers immune-metabolic dysfunction in KOA, with HomC acting as a hub for FGF-mediated synovitis and ECM remodeling. The diagnostic model and regulon network ( SREBF1/YY1 ) offer translational tools for early detection, while impaired mast cell homeostasis highlights novel immunotherapeutic targets. Our findings bridge ferroptosis, immune dysregulation, and metabolic stress, advancing precision strategies for KOA management.

Correction to “Tumor Necrosis Factor‐α Promotes the Lymphangiogenesis of Gallbladder Carcinoma Through Nuclear Factor‐<scp>κB</scp>‐Mediated Upregulation of Vascular Endothelial Growth Factor‐C”

2025-06-25

| Cancer Science

The PURB–HOTAIR complex regulates p53-dependent promoter-specific transcriptional activation

2025-06-25

Zhangchuan Xia , Ning Kon , Zhenyi Su +5 more | Nature Structural & Molecular Biology

Expression of SOX10, and micro-RNA 221 and Micro-RNA 222 in Oral Squamous Cell Carcinoma and Correlation with Clinicopathological Characteristics

2025-06-25

Soroor Shahedi , Narges Gholizadeh , Hadiseh Mohammadpour +2 more | Head and Neck Pathology

Identification of core noncoding RNA-associated competing endogenous RNA networks in renal fibrosis via whole-transcriptome sequencing

2025-06-25

Yizhen Chen , Meng Cheng , Rong Dai +7 more | Renal Failure

This study aimed to investigate noncoding RNA (ncRNA) expression changes in renal fibrosis (RF) models induced by three distinct etiologies using whole-transcriptome RNA sequencing, identify overlapping differentially expressed (DE) ncRNAs, … This study aimed to investigate noncoding RNA (ncRNA) expression changes in renal fibrosis (RF) models induced by three distinct etiologies using whole-transcriptome RNA sequencing, identify overlapping differentially expressed (DE) ncRNAs, construct core competing endogenous RNA (ceRNA) networks, and explore their role in RF. Three RF rat models, 5/6 nephrectomy, adenine, and unilateral ureteral obstruction, were established. DE RNAs were identified through sequencing and validated by real-time quantitative polymerase chain reaction. ceRNA and RNA-binding protein (RBP) networks were visualized using Cytoscape. Core ceRNA axes were validated with dual-luciferase assay, RNA fluorescence in situ hybridization, western blot, immunofluorescence, and immunohistochemistry. Enrichment analysis was performed to explore potential functions. Sequencing analysis revealed significant dysregulation of ncRNAs in all models compared to the normal group. Intersection analysis identified 215 mRNAs, 19 lncRNAs, and 247 circRNAs as overlapping DE RNAs. lncRNA-based ceRNA networks comprising 7 lncRNAs, 8 miRNAs, and 21 mRNAs, and circRNA-based networks comprising 13 circRNAs, 29 miRNAs, and 41 mRNAs were constructed. The TCONS_00008870/circRNA_3140-miR-466b-3p-Adamts2 axis was identified as a key regulatory pathway. Enrichment analysis showed significant pathways including Rap1 signaling, extracellular matrix-receptor interaction, and PI3K-Akt signaling, with RBPs enriched in RNA binding and ferroptosis. By integrating data from three distinct models, we identified conserved ceRNA axis-TCONS_00008870/circRNA_3140-miR-466b-3p-Adamts2-potentially modulating fibrotic progression in renal tissue.

Identification and Analysis of Differentially Expressed Ferroptosis-Related Genes in Microtia

2025-06-25

Jingyang Zhou , Runmeng Cui , Lin Lin | Journal of Craniofacial Surgery

Microtia is a congenital auricle deformity that might be caused by the abnormal development of the auricular cartilage during the pregnancy. The ferroptosis has been identified to be associated with … Microtia is a congenital auricle deformity that might be caused by the abnormal development of the auricular cartilage during the pregnancy. The ferroptosis has been identified to be associated with quite number of diseases related to the cartilage. So the aim of this study is to reveal the genetic relationship between the microtia and the ferroptosis through an approach of bioinformatics analysis and provide inspiration for subsequent research in this field. In this study, the online gene expression profile GSE242921, along with the FerrDB database, was utilized to screen the differentially expressed genes related to the ferroptosis in microtia. The top 10 differentially expressed ferroptosis-related genes identified in this analysis are STAT3, CDH1, HRAS, CDKN2A, SLC1A5, PTPN6, DDR2, FURIN, SMAD7, and IFNA6, and the transcription factors with degree no <5 of aforementioned genes are FOXC1, USF2, GATA2, CREB1, E2F1, and TFAP2A. In general, there is a close and non-negligible link between ferroptosis and microtia at the genetic level, but the genetic mechanisms underlying the role of ferroptosis in the pathogenetic process of microtia still need more experimental data to determine.

The lncRNA Gas5 is an activity-responsive scaffold that mediates cAMP-dependent synaptic plasticity

2025-06-24

Kaushik Chanda , Eddie Grinman , Kaylyn Clark +4 more | Science Signaling

Changes in the transcriptome are critical in shaping the structural plasticity of neurons, which underpins learning and long-term memory storage. Here, we explored the effect of two opposing, plasticity-associated pathways-cAMP … Changes in the transcriptome are critical in shaping the structural plasticity of neurons, which underpins learning and long-term memory storage. Here, we explored the effect of two opposing, plasticity-associated pathways-cAMP second-messenger signaling and metabotropic glutamate receptor (mGluR1 and mGluR5) signaling-on the transcriptome in hippocampal neurons and how these pathways operate in distinct and coordinated manners to induce structural changes. Integration of transcriptome data and molecular pathway analysis identified central "hub" genes that were rapidly induced by cAMP and/or mGluR1/5 in hippocampal neurons. These included the long noncoding RNA (lncRNA) Gas5, whose expression was induced specifically by cAMP and which was targeted to dendrites by the kinesin motor protein KIF1A. In the dendrites, Gas5 interacted with various proteins and coding and noncoding RNAs associated with synaptic function and plasticity, and these interactions were altered by cAMP signaling. Gas5 interacted with the microRNA miR-26a-5p and sequestered it from several of its mRNA targets associated with neuronal function and whose translation was induced by cAMP. Gas5 was critical for excitatory synaptic transmission induced by cAMP but not those induced by mGluR1/5. Furthermore, Gas5 deficiency impaired dendritic branching and synapse morphology, and Gas5 abundance was decreased in the hippocampus of a mouse model of Alzheimer's disease. Together, these findings provide insight into the transcriptional networks involved in synaptic plasticity and a lncRNA interactome that mediates dendritically localized regulation of excitatory synaptic transmission and neuronal architecture.

m5C-Modified lncRNA SNHG15 Promotes Ovarian Cancer Progression Via the miR-545-3p/PD-L1 Axis

2025-06-24

Li Chen , Ran‐Ran Ma , Lei Wu +3 more | Reproductive Sciences

Uncovering novel lncRNAs linked to melanoma growth and migration with CRISPR-inhibition screening

2025-06-24

Stavroula Petroulia , Kathryn Hockemeyer , Sudhanshu Tiwari +7 more | Cancer Research Communications

Melanoma being one of the most common and deadliest skin cancers, has been rising since the past decade. Patients at advanced stages of the disease have very poor prognoses, as … Melanoma being one of the most common and deadliest skin cancers, has been rising since the past decade. Patients at advanced stages of the disease have very poor prognoses, as opposed to at the earlier stages. Nowadays the standard-of-care of advanced melanoma is resection followed by immune checkpoint inhibition based immunotherapy. However, a substantial proportion of patients either do not respond or develop resistances. This underscores a need for novel approaches and therapeutic targets as well as a better understanding of the mechanisms of melanoma pathogenesis. Long non-coding RNAs (lncRNAs) comprise a poorly characterized class of functional players and promising targets in promoting malignancy. Certain lncRNAs have been identified to play integral roles in melanoma progression and drug resistances, however systematic screens to uncover novel functional lncRNAs are scarce. Here, we profile differentially expressed lncRNAs in patient derived short-term metastatic cultures and BRAF- MEK-inhibition resistant cells. We conduct a focused growth-related CRISPR-inhibition screen of overexpressed lncRNAs, validate and functionally characterize lncRNA hits with respect to cellular growth, invasive capacities and apoptosis in vitro as well as the transcriptomic impact of our lead candidate the novel lncRNA XLOC_030781. In sum, we extend the current knowledge of ncRNAs and their potential relevance on melanoma.

An EGFR Co-Amplified and De Novo Long Noncoding RNA HELDR Promotes Glioblastoma Malignancy through KAT7-Driven Gene Programs

2025-06-24

Shi‐Yuan Cheng , Xiaozhou Yu , Xiao Song +7 more

<title>Abstract</title> EGFR amplification frequently happens within extrachromosome DNAs (ecDNAs) and is a major mutation in glioblastoma (GBM). However, targeting EGFR for GBM treatments has been unsuccessful. Here we characterized a … <title>Abstract</title> EGFR amplification frequently happens within extrachromosome DNAs (ecDNAs) and is a major mutation in glioblastoma (GBM). However, targeting EGFR for GBM treatments has been unsuccessful. Here we characterized a long non-coding RNA (lncRNA) that is co-amplified with EGFR within ecDNAs that we name hidden EGFR long non-coding downstream RNA (HELDR). HELDR is a GBM-specific lncRNA that promotes tumorigenicity independent of EGFR signaling. HELDR globally binds genomic DNA and recruits the transcription co-activator p300 to the KAT7 promoter. p300-induced H3K27ac at the KAT7 promoter enlists other co-transcription factors, activating KAT7 transcription. KAT7 induces H3K14ac and H4K12ac that activate KAT7-driven gene programs that are critical for GBM malignancy. Targeting KAT7 or HELDR markedly enhances therapeutic effects of anti-EGFR treatments for GBM. These results not only reveal the role of HELDR in EGFR-driven GBM but also provide a strong rationale to characterize the role of lncRNAs co-amplified with driver oncogenes in human cancers.

LncRNA ST6GALNAC3 inhibits dermal fibroblast proliferation and migration in cashmere goat hair follicles via chi-miR-24-3p/ID4 axis

2025-06-24

Rong Ma , Qing Ma , Lu Zhang +7 more | Animal Bioscience

Exploring lncRNA-Mediated Mechanisms in Muscle Regulation and Their Implications for Duchenne Muscular Dystrophy

2025-06-24

Abdolvahab Ebrahimpour Gorji , Zahra Roudbari , Kasra Ahmadian +4 more | International Journal of Molecular Sciences

Duchenne muscular dystrophy (DMD) manifests as a hereditary condition that diminishes muscular strength through the progressive degeneration of structural muscle tissue, which is brought about by deficiencies in the dystrophin … Duchenne muscular dystrophy (DMD) manifests as a hereditary condition that diminishes muscular strength through the progressive degeneration of structural muscle tissue, which is brought about by deficiencies in the dystrophin protein required for the integrity of muscle cells. DMD is among four different types of dystrophinopathy disorders. Current studies have established that long non-coding RNAs (lncRNAs) play a significant role in determining the trajectory and overall prognosis of chronic musculoskeletal conditions. LncRNAs are different in terms of their lengths, production mechanisms, and operational modes, but they do not produce proteins, as their primary activity is the regulation of gene expression. This research synthesizes current literature on the role of lncRNAs in the regulation of myogenesis with a specific focus on certain lncRNAs leading to DMD increments or suppressing muscle biological functions. LncRNAs modulate skeletal myogenesis gene expression, yet pathological lncRNA function is linked to various muscular diseases. Some lncRNAs directly control genes or indirectly control miRNAs with positive or negative effects on muscle cells or the development of DMD. The research findings have significantly advanced our knowledge about the regulatory function of lncRNAs on muscle growth and regeneration processes and DMD diseases.

miRTARGET: An integrated web tool for the identification of microRNA targets with potential therapeutic or prognostic value in cancer

2025-06-24

Matjaž Rokavec , Heiko Hermeking | Neoplasia

Prognostic value of a lncRNA signature in early-stage invasive breast cancer patients

2025-06-24

Rong Guo , Xiting Wang , Yinju Yang +7 more | Cancer Cell International

Integrative Multi-Omic and Immune Profiling of Lung Adenocarcinoma: Molecular Landscapes, Gene Expression, and Treatment Response Insights

2025-06-24

Yahui Tian , Honghong Dong , Yujie Guo +5 more | The Oncologist

Abstract Background Lung adenocarcinoma (LUAD) is a major cause of cancer death. Traditional histopathological classification overlooks molecular heterogeneity, limiting personalized treatment. This study used multiomic data to define LUAD subtypes, … Abstract Background Lung adenocarcinoma (LUAD) is a major cause of cancer death. Traditional histopathological classification overlooks molecular heterogeneity, limiting personalized treatment. This study used multiomic data to define LUAD subtypes, assess prognostic significance, and analyze immune features, aiming to improve targeted therapy and clinical outcomes. Methods This study used Consensus Clustering and Gap Statistics to analyze LUAD multiomic data, including mRNA, lncRNA, miRNA, DNA methylation, and mutations. Clustering was validated by silhouette plots and heatmaps. Molecular characterization involved regulon activity, immune and metabolic profiling. Functional assays (qPCR, WB, CCK-8, flow cytometry) assessed NDNF’s role in LUAD. Results Two molecular LUAD subtypes showed distinct clustering and survival outcomes. One subtype had worse prognosis and unique immune features, including checkpoint expression and microenvironment differences. Gene signatures and metabolism varied by subtype. NDNF was downregulated in tumors; its overexpression suppressed LUAD cell viability and promoted apoptosis, suggesting tumor-suppressive function. Conclusion This study identifies two LUAD subtypes with distinct molecular and immune features linked to prognosis and therapy response. NDNF downregulation and its tumor-suppressive effects highlight its therapeutic potential. These findings support improved LUAD stratification and personalized treatment strategies. Implications for Practice This study reveals two LUAD molecular subtypes with distinct prognoses and immune features, offering a basis for more precise treatment strategies. The identification of NDNF as a potential tumor suppressor suggests its value as both a biomarker and therapeutic target. These findings support improved LUAD stratification and personalized therapy.

Correction to “<scp>lncRNA XLOC013218</scp> Promotes Cell Proliferation and <scp>TMZ</scp> Resistance by Targeting the <scp>PIK3R2</scp>‐Mediated <scp>PI3K</scp>/<scp>AKT</scp> Pathway in Glioma”

2025-06-23

| Cancer Science

Prognostic and therapeutic implications of lipid metabolism-related lncRNAs in lung adenocarcinoma: a comprehensive analysis integrating transcriptomics, Mendelian randomization, and immunotherapy sensitivity

2025-06-23

Xiao Zhu | Clinical Cancer Bulletin

Abstract Background and Aim Lipid metabolism plays a crucial role in cancer progression, and long non-coding RNAs (lncRNAs) are emerging as key regulators in tumor biology. However, the prognostic and … Abstract Background and Aim Lipid metabolism plays a crucial role in cancer progression, and long non-coding RNAs (lncRNAs) are emerging as key regulators in tumor biology. However, the prognostic and therapeutic implications of lipid metabolism-related lncRNAs in lung adenocarcinoma (LUAD) remain unclear. This study aimed to identify lipid metabolism-associated lncRNAs, construct a prognostic model, and explore their clinical relevance in LUAD. Methods Transcriptomic and clinical data from LUAD patients were obtained from The Cancer Genome Atlas (TCGA). Co-expression networks, functional enrichment (GO/KEGG), and survival analyses (univariate/multivariate Cox regression, LASSO) were used to identify prognostic lncRNAs. A risk prediction model was developed and validated using tumor mutation burden (TMB), immune microenvironment analysis, and drug sensitivity profiling. Mendelian randomization (MR) and Bayesian weighting were employed to assess causal relationships between lipid metabolism pathways and LUAD. Results Three lipid metabolism-related lncRNAs—LINC00862 and AC125807.2 (risk factors) and LINC01447 (protective factor)—were significantly associated with LUAD prognosis. The risk model stratified patients into high- and low-risk groups with distinct sur-vival outcomes ( p < 0.001). High-risk patients exhibited elevated TMB and immune dysfunction but greater sensitivity to chemotherapy (e.g., cisplatin, gemcitabine), while low-risk patients showed potential responsiveness to targeted therapies (e.g., PAK1/GSK-3 inhibitors). MR analysis confirmed that normal lipid metabolism pathways (linoleic acid/fatty acid metabolism) reduce LUAD risk (IVW p < 0.05). Conclusion This study identifies lipid metabolism-related lncRNAs as novel prognostic biomarkers in LUAD, with implications for risk stratification and personalized therapy. The findings highlight the interplay between lipid metabolism, immune regulation, and therapeutic response, offering a foundation for future clinical validation and targeted interventions.

LncRNA TRPM2-AS promotes cell proliferation, migration, and invasion by regulating the miR-195-5p/COP1 axis in bladder cancer

2025-06-23

Changyuan Dai , Qingwen Li , Lili Wang +3 more | Naunyn-Schmiedeberg s Archives of Pharmacology

LINC01013 reverses bisphosphonate-impaired osteogenic differentiation of JBMMSCs by regulating intracellular translocation of ILF3

2025-06-23

Jiaxin Song , Wanqing Wang , Xuanhe Feng +3 more | Stem Cell Research & Therapy

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate (BP) therapy. Enhancement of the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (JBMMSCs) is … Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate (BP) therapy. Enhancement of the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (JBMMSCs) is a key issue in the treatment of BRONJ. In this study, we investigated the role and mechanism of LINC01013 in regulating osteogenic differentiation of JBMMSCs. Osteogenic differentiation of JBMMSCs was assessed in vitro using alkaline phosphatase (ALP), alizarin red staining (ARS), and western blotting. JBMMSCs transplanted into the backs of nude mice were used to detect JBMMSCs osteogenesis in vivo. Molecular mechanisms involved in JBMMSCs osteogenesis were evaluated using real-time fluorescence quantitative polymerase chain reaction, western blotting, fluorescence in situ hybridization, RNA pull-down, and RNA-seq. Homeobox C8 (HOXC8) knockdown enhanced ALP activity, ARS, and expression of bone sialoprotein and osteocalcin in JBMMSCs under normal and BP stimulation conditions. HOXC8 negatively regulated LINC01013 expression. LINC01013 enhanced JBMMSCs osteogenic differentiation impaired by BP stimulation. Furthermore, LINC01013 regulated the expression of inflammation-related genes in JBMMSCs under BP conditions. LINC01013 formed a complex with ILF3. Two isoforms of ILF3 (NF90 and NF110) promoted the osteogenic differentiation of JBMMSCs under normal and BP conditions, depending on their nuclear localization. Additionally, NF90, which is located in the nucleus, inhibited the expression of NLR family pyrin domain containing 3 (NLRP3). In summary, HOXC8 negatively regulates LINC01013 to inhibit osteogenic differentiation of JBMMSCs under BP conditions. We also further clarified that LINC01013 binding to ILF3 affects ILF3 nuclear localization to regulate JBMMSCs osteogenic differentiation and regulates NLRP3/Caspase-1 pathway to affect JBMMSCs function under BP stimulation.

Construing the role of risk factor-induced oral microbiome dysbiosis in manipulation of lncRNA involved in oral cancer

2025-06-23

Manish Kumar Mishra , Sachin Gupta , Preeti Rani +3 more | Indian Journal of Otolaryngology and Head & Neck Surgery

MLWNNR: LncRNA-Disease Association Prediction with Multi-Kernel Learning-Driven Weighted Nuclear Norm Regularization

2025-06-23

Guobo Xie , Haojie Xu , Guosheng Gu +3 more | Interdisciplinary Sciences Computational Life Sciences

LncRNA Foxo6os as a Novel “ Scaffold” Mediates MYBPC3 in Combating Pathological Cardiac Hypertrophy and Heart Failure

2025-06-23

Jie Sheng , Qin Lin , Yizhuo Sun +7 more | Advanced Science

Heart failure (HF) as the terminal stage of various cardiac diseases, its underlying molecular mechanisms still remain elusive. Emerging evidence have implicated long noncoding RNAs (lncRNAs) play a multifaceted role … Heart failure (HF) as the terminal stage of various cardiac diseases, its underlying molecular mechanisms still remain elusive. Emerging evidence have implicated long noncoding RNAs (lncRNAs) play a multifaceted role in the progression of cardiac hypertrophy and HF. Here, it is identified that a lncRNA forkhead box O6, opposite strand (Foxo6os) is significantly downregulated in murine HF model induced using transverse aortic constriction (TAC). Knockdown of Foxo6os accelerates cardiomyocyte hypertrophy, reflects as elevated expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and myosin heavy chain 7 (MYH7). Conversely, Foxo6os overexpression can improve cardiac function and alleviate adverse cardiac remodeling. Mechanistically, Foxo6os directly interacts with myosin-binding protein-C (MYBPC3), which then recruits protein kinase C alpha (PKC-α) to facilitate MYBPC3 phosphorylation, resulting in maintaining myocardial contractility and postponing HF progression. Therefore, these findings underscore the critical role of Foxo6os in preserving cardiomyocyte contractile function, suggesting a potential for Foxo6os as a novel therapeutic target of HF.

Innate immunity and the NF-κB pathway control prostate stem cell plasticity, reprogramming and tumor initiation

2025-06-23

Chunying Chen , Yura Song , Sandrine Rorive +7 more | Nature Cancer

Non-coding RNAs as key regulators in hepatitis B virus-related hepatocellular carcinoma

2025-06-23

Prasanna Srinivasan Ramalingam , L. Zhang , Md Sadique Hussain +6 more | Frontiers in Immunology

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a significant global health challenge due to its high prevalence and poor prognosis. Recent advances have revealed that non-coding RNAs (ncRNAs), including … Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a significant global health challenge due to its high prevalence and poor prognosis. Recent advances have revealed that non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs, circular RNAs, and small nucleolar RNAs, play critical regulatory roles in HBV-induced oncogenesis. These ncRNAs modulate various cancer hallmarks and contribute to HCC progression. Notably, their stability, detectability in bodily fluids, and disease-specific expression patterns render these ncRNAs as highly promising diagnostic and prognostic biomarkers for HBV-HCC. Herein, we review the types and mechanisms of HBV-related ncRNAs, emphasizing their dual roles as oncogenes and tumor suppressors. Furthermore, we discuss their applicability as diagnostic markers and therapeutic targets and review recent directions in ncRNA-based approaches that aim to enhance patient treatment. Concerning these aspects, the present review aimed to provide an understanding of the complexity of ncRNAs in HBV-related HCC with the hope of directing future research and developments towards effective control of this complex malignancy known as HCC.

Comprehensive Expression of Long non-coding RNAs and association with the Iron and Erythropoiesis Regulatory Proteins in Transfusion-dependent β-Thalassemia

2025-06-22

Ola M. Al-Sanabra , Wafa' J. Haza , Abeer A. Haza'a +4 more | Archives of Medical Science

Introduction β-Thalassemia is a genetic disorder characterized by a quantitative defect in β-globin synthesis caused by genetic and epigenetic alterations. However, the expression patterns of long non-coding RNAs (LncRNAs) and … Introduction β-Thalassemia is a genetic disorder characterized by a quantitative defect in β-globin synthesis caused by genetic and epigenetic alterations. However, the expression patterns of long non-coding RNAs (LncRNAs) and their relationship with genes and proteins involved in iron metabolism and erythropoiesis remain largely unknown. We aimed to investigate the expression of LncRNAs and their correlation with iron and erythropoiesis regulatory proteins in patients with transfusion dependent-β-Thalassemia (TDβ-T). Material and methods Whole blood samples and clinical records were collected from 60 patients with TDβ-T and 20 healthy controls. Expression levels of selected LncRNAs were measured using qRT-PCR. Iron metabolism and erythropoiesis-related proteins were quantified using ELISA. Results TDβ-T patients exhibited significantly elevated levels of iron and erythropoiesis-regulating proteins, as well as increased expression of HAMP, GDF-15, FAM132B, and SLC40A1 compared to controls. Additionally, LncRNAs ANRIL, H9, LINCO133, MIAT, and NEAT1 were markedly upregulated, while LncRNA GAS5 was downregulated in patients with TDβ-T. Among these, LncRNAs NEAT1 and GAS5 showed the strongest diagnostic performance. A significant correlation was observed between the expression of HAMP and FAM132B and LncRNAs ANRIL, H19, LINCO133, and MIAT. Furthermore, LncRNA NEAT1 expression correlated positively with SLC40A1 and negatively with urea levels, whereas LncRNA GAS5 was inversely correlated with HAMP expression. Conclusions This study is the first to demonstrate altered LncRNA expression patterns and their associations with iron metabolism, erythropoiesis-regulating proteins, and urea levels in patients with TDβ-T. These findings provide new insights for future research and potential therapeutic targets.

The role of the NcRNA/ferroptosis axis in lung cancer: molecular mechanisms and potential therapeutic targets

2025-06-22

Mina Alimohammadi , Samaneh Kahkesh , William C. Cho +7 more | APOPTOSIS

Unraveling hereditary breast cancer susceptibility: a systems biology approach on GEO datasets with functional genomic insights and implications for traditional Chinese medicine

2025-06-22

Elham Amjad , Babak Sokouti | Egyptian Journal of Medical Human Genetics

Abstract Background This study aimed to identify the genetic causes of hereditary breast cancer and potential treatment strategies by combining genomic and traditional Chinese medicine investigations. Of the many genes … Abstract Background This study aimed to identify the genetic causes of hereditary breast cancer and potential treatment strategies by combining genomic and traditional Chinese medicine investigations. Of the many genes that significantly increase the risk of developing breast cancer, BRCA1 and BRCA2 are primarily responsible for the majority of hereditary breast cancers. Results Following a systematic review and analysis using Gene Expression Omnibus datasets and various systems biology tools, we identified 16 important differentially expressed genes. These include ZEB1, FOXP1, ETS1, and BCL2, all of which play a role in tumorigenesis through apoptosis, cell proliferation, and metastasis. This study shows how hub genes work with herbs, which helps us learn more about how traditional Chinese medicine can be used to treat illness. Resveratrol, cinobufagin, brusatol, and oxymatrine are examples of these herbs. All of these have been shown to affect the functioning of cancer cells. Based on enrichment analysis, some of these herbs may boost the immune system and stop tumor growth. Conclusions Genomic information, alternative medicine, and personalized medicine can be used for breast cancer treatment. By providing a different treatment option that works with standard medicine, this method can improve precision medicine for people whose family history increases their risk of developing breast cancer. For integrative approaches to be successful and safe, they must be tested in more clinical settings.

PANDORA-Seq Unveils the Hidden Small Non-Coding RNA Landscape in Hypopharyngeal Carcinoma

2025-06-21

Minya Pu , L. Y. Shi , Haiyu Ma +4 more | International Journal of Molecular Sciences

Hypopharyngeal carcinoma is a highly aggressive malignancy in the head and neck region with poor prognosis due to challenges in early diagnosis, high invasiveness, recurrence rate, and metastatic potential. Small … Hypopharyngeal carcinoma is a highly aggressive malignancy in the head and neck region with poor prognosis due to challenges in early diagnosis, high invasiveness, recurrence rate, and metastatic potential. Small non-coding RNAs (sncRNAs) play crucial roles in tumorigenesis and progression and hold potential as clinical diagnostic biomarkers and therapeutic targets. However, the ability of traditional RNA-sequencing technologies to detect modified sncRNAs is limited, potentially leading to the failure to accurately identify some functionally relevant sncRNAs. In this study, we employed PANDORA-seq technology for the first time to systematically profile sncRNA expression in cancerous and adjacent normal tissues from five patients with hypopharyngeal carcinoma. Our results revealed dynamic changes in sncRNA expression in hypopharyngeal carcinoma tissues and found 4798 significantly differentially expressed sncRNAs. Among these, differentially expressed miRNAs and tsRNAs were primarily involved in key signaling pathways, including MAPK, FoxO, and TGF-β. Additionally, we validated the differential expression of eight sncRNAs in hypopharyngeal carcinoma tissues, which may represent potential diagnostic biomarkers and therapeutic targets. This study lays the foundation for the application of PANDORA-seq technology in human cancers and offers new directions for exploring the underlying molecular mechanisms of hypopharyngeal carcinoma and potential targets for its clinical diagnosis and treatment.

The Tissue Expression Divergence of the WUSCHEL-Related Homeobox Gene Family in the Evolution of Nelumbo

2025-06-21

Juanjuan Li , Yue Zhang | Plants

The yellow flower lotus (Nelumbo lutea) is the sister species of the sacred lotus (N. nucifera). The evolution of gene expression patterns across multiple tissues during the species divergence of … The yellow flower lotus (Nelumbo lutea) is the sister species of the sacred lotus (N. nucifera). The evolution of gene expression patterns across multiple tissues during the species divergence of these two lotuses remains unexplored. The WUSCHEL-related homeobox (WOX) family, a plant-specific transcription factor family, plays a crucial role in tissue development and stress responses. In this study, utilizing a chromosome-level reference genome and a transcriptome database covering multiple tissues, we identified and categorized 11 NlWOX genes into three subfamilies. We identified seven syntenic gene pairs between NnWOXs and NlWOXs that originated from whole-genome duplications. Through conserved motif analysis, we found subfamily-specific motifs in the protein sequences of NnWOXs and NlWOXs. Variations in the three-dimensional conformations of homologous WOX genes indicate function divergences between the two lotus species. The gene expression matrix of NlWOX across tissues reveals expression divergences within N. lutea and between the two lotus species. By employing a weight gene co-expression network analysis pipeline, we developed eight NlWOX co-expression networks that differed from the co-expression networks of their syntenic genes. Overall, our findings suggest that genomic variations in the WOX orthologs contribute to the distinct expression patterns and regulatory networks observed during the evolution of these two lotuses.

Tanshinone IIA inhibits neuronal ferroptosis and relieves cerebral ischemia‒reperfusion injury by regulating miR-449a/ACSL4

2025-06-21

Huimin Yu , Yili Li , Yinchuang Yang +7 more | Metabolic Brain Disease

Improved gut microbiota by selenium-enriched Bifidobacterium longum DD98 alleviates chemotherapy-induced intestinal mucositis via inhibiting the STING pathway

2025-06-21

Yunping Qiu , Chen Ye , Qiao Li +6 more | npj Science of Food

Intestinal mucositis, a common chemotherapy side effect, lacks effective treatments. This study evaluated the protective effect of selenium-enriched Bifidobacterium longum DD98 (SeDD98) on irinotecan-induced intestinal mucositis. Irinotecan caused intestinal mucositis, … Intestinal mucositis, a common chemotherapy side effect, lacks effective treatments. This study evaluated the protective effect of selenium-enriched Bifidobacterium longum DD98 (SeDD98) on irinotecan-induced intestinal mucositis. Irinotecan caused intestinal mucositis, characterized by weight loss, severe diarrhea, damaged intestinal structure, reduced tight junction proteins, and gut dysbiosis. These effects could be inhibited by SeDD98. Additionally, fecal microbiota from SeDD98-treated mice protected against intestinal mucositis. Mechanistically, irinotecan activated the stimulator of interferon genes (STING) / nuclear factor kappa-B (NF-κB) pathway, whereas SeDD98 and fecal microbiota from SeDD98-treated mice suppressed this activation. Furthermore, depletion of gut microbiota by a broad-spectrum antibiotic cocktail (ABX) blunted the protective effect of SeDD98 and its inhibition of the STING/NF-κB pathway. These findings suggest that SeDD98 could protect against intestinal mucositis via inhibiting the STING/NF-κB pathway, likely through improving gut microbiota. Overall, SeDD98 may be a potential therapeutic agent for preventing chemotherapy-induced intestinal mucositis via gut microbiome improvement.

LINC00601 promotes the progression of glioma via the p-STAT3 signaling pathway

2025-06-21

Chao Ma , Linqi Wang , Renwu Zhang +5 more | Cancer Cell International

Gliomas, the most common malignant tumors of the central nervous system, primarily originate from glial cells, which support nerve cells. Due to their high malignancy and aggressiveness, gliomas frequently result … Gliomas, the most common malignant tumors of the central nervous system, primarily originate from glial cells, which support nerve cells. Due to their high malignancy and aggressiveness, gliomas frequently result in poor prognoses. Increasing evidence suggests that long non-coding RNAs (lncRNAs) have diverse roles in cancer; however, their specific functions in gliomas remain poorly understood. This study elucidates the roles and potential mechanisms of the lncRNA LINC00601 in glioma. Bioinformatics analysis was utilized to identify the expression of LINC00601 and to perform related survival analysis. Glioma cells were transfected with a control vector small interfering RNA (si-NC) or small interfering RNA LINC00601 (si-LINC00601). Cell proliferation was evaluated using the CCK-8 assay and plate colony formation assay. Cell migration and invasion were assessed using the Transwell assay. Protein expression was detected by Western blot analysis, and lncRNA levels were measured using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis revealed that LINC00601 is associated with the pathological grade and prognosis of glioma, as evidenced by data from the TCGA and CGGA databases. In vivo experiments showed that LINC00601 knockdown inhibits the proliferation, migration, and invasion of U251 and U87 cells. Based on sequencing and Western blot results, this effect is thought to be linked to changes in Phosphorylated Signal Transducer and Activator of Transcription 3 (p-STAT3) expression. Additionally, in vitro knockdown of LINC00601 has been shown to inhibit glioma growth. LINC00601, which facilitates glioma progression by modulating the p-STAT3 signaling pathway, could serve as a potential molecular target for glioma therapy.

A novel approach to enhance glioblastoma multiforme treatment efficacy: non-coding RNA targeted therapy and adjuvant approaches

2025-06-21

Ming Liu , Yuying Wang , Xiaoli Chen +7 more | Clinical Epigenetics

Abstract Background Glioblastoma multiforme (GBM) is a lethal brain tumor. With the current gold standard chemotherapy treatment, temozolomide (TMZ), many patients do not survive beyond one year. While the urgency … Abstract Background Glioblastoma multiforme (GBM) is a lethal brain tumor. With the current gold standard chemotherapy treatment, temozolomide (TMZ), many patients do not survive beyond one year. While the urgency of researching novel treatments is understandable, the prohibitively high costs and the prolonged duration of research and clinical trials significantly delay the availability of medical advancements to the general public. This highlights the urgent need for adjuvant therapies to enhance treatment effectiveness. Main body: Recent research has suggested the potential of repurposing FDA-approved drugs such as temozolomide (TMZ), disulfiram (DSF), and aspirin for the treatment of glioblastoma, with encouraging evidence particularly for DSF and aspirin. Additionally, compounds like histone deacetylase inhibitors (e.g., vorinostat) are being investigated for their impact on non-coding RNA (ncRNA) modulation, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Combining traditional therapies with ncRNA modulation has shown potential in enhancing therapeutic efficacy and targeting specificity. NcRNAs play a crucial role in regulating gene expression and have been implicated in tumor growth, invasion, and treatment resistance. Recent discoveries, such as cuproptosis, offer new insights into tumor cell death mechanisms. Conclusion This review focuses on how these molecular insights can serve as novel therapeutic targets and how drug adjuvant therapy may improve GBM treatment strategies. It focuses on how the integration of ncRNA modulation with conventional therapies and the combination strategy of enhancing efficacy of drugs can enhance treatment efficacy and pave the way for innovative approaches in managing GBM. In short, we will explore how non-coding RNAs (ncRNAs) might serve as promising targets and how repurposing TMZ, DSF, and aspirin could help enhance the efficacy of GBM treatment. Graphical abstract

Influence of migrasome-associated long noncoding RNAs on the immune microenvironment and prognosis in lung adenocarcinoma

2025-06-20

Hui Zhao , Kunpeng Yang , Yue‐Jiao Lan +7 more | Discover Oncology

This study investigated the prognostic impact of migrasome-related long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD). We analyzed transcriptomic data from The Cancer Genome Atlas (TCGA) database, comprising 541 tumor … This study investigated the prognostic impact of migrasome-related long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD). We analyzed transcriptomic data from The Cancer Genome Atlas (TCGA) database, comprising 541 tumor samples and 59 normal tissue samples, to pinpoint key migrasome genes and related lncRNAs, using correlation analysis to detect those pertinent to patient outcomes. A risk score model based on 17 migrasome-related lncRNAs, constructed via univariate, LASSO, and multivariate Cox regression, was then validated in an independent dataset to ensure reliability. Our findings revealed that high-risk patients exhibited worse overall and progression-free survival, alongside altered immune features, such as potential immune evasion and an increased propensity for immunotherapy responsiveness. Moreover, Tumor Immune Dysfunction and Exclusion (TIDE) analyses suggested that individuals with higher scores could experience greater benefit from immune checkpoint inhibitors. Functional enrichment analysis supported the engagement of migrasome-related pathways and immune-regulatory processes that may drive disease progression. Additionally, principal component analysis (PCA) confirmed the robustness of our lncRNA-driven classifier, enabling accurate differentiation of risk cohorts. Overall, our study underscores the contribution of migrasome-related lncRNAs in predicting LUAD prognosis and informing clinical choices, shedding light on tumor biology and immunotherapy response. These results emphasize the clinical importance of migrasome-related lncRNAs as promising therapeutic targets and prognostic biomarkers in LUAD management.

Correction: E2F7−EZH2 axis regulates PTEN/AKT/mTOR signalling and glioblastoma progression

2025-06-20

Rui Yang , Mei Wang , Guanghui Zhang +5 more | British Journal of Cancer

The lincRNA <i>Pantr1</i> is a FOXG1 target gene conferring site-specific chromatin binding of FOXG1

2025-06-20

Fabian Gather , Tudor Rauleac , Ipek Akol +7 more | PubMed

Derailed gene expression programs within the developing nervous system, encompassing both transcriptional and post-transcriptional processes, can cause diverse neurodevelopmental diseases (NDD). The NDD FOXG1-syndrome lacks full understanding of the mechanistic … Derailed gene expression programs within the developing nervous system, encompassing both transcriptional and post-transcriptional processes, can cause diverse neurodevelopmental diseases (NDD). The NDD FOXG1-syndrome lacks full understanding of the mechanistic role of its eponymous gene product. While it is known that FOXG1 acts in part at the chromatin by binding to regulative regions, it is unclear what factors control its presence at specific sites. Long non-coding RNAs (lncRNAs) can mediate site-directed transcription factor binding, but their potential role in FOXG1-syndrome has not been described. Here, we show that FOXG1 localisation is regulated at selected loci through the lncRNA Pantr1. We identified FOXG1 as an upstream transcriptional activator of Pantr1 in human and mice. Further, we discovered that FOXG1 has the ability to associate with RNAs. Both transcriptional regulation of Pantr1 by FOXG1 and binding of both partners build up a regulative network that impacts the localisation of FOXG1 at selected genomic loci. Specifically, Pantr1 facilitates cooperative presence of FOXG1/NEUROD1 at specific sites, and Pantr1 reduction leads to redistribution of FOXG1 to comparably more generic binding sites. The rescue of impaired dendritic outgrowth upon FOXG1 reduction by simultaneous overexpression of Pantr1 underlines the importance of the FOXG1/Pantr1 regulative network.

The role of notch signaling pathway and non-coding RNAs in cancer and inflammation: progress, therapeutic insights, and future directions

2025-06-20

Rong-zu Nie , Hang Wang , Shuangshuang Wang +5 more | Frontiers in Immunology

The Notch signaling pathway and non-coding RNAs (ncRNAs) play significant roles in regulating key cellular processes such as cancer progression, metastasis, and drug resistance. This article systematically reviews the interactions … The Notch signaling pathway and non-coding RNAs (ncRNAs) play significant roles in regulating key cellular processes such as cancer progression, metastasis, and drug resistance. This article systematically reviews the interactions between the Notch pathway and ncRNAs including miRNAs, lncRNAs, and circRNAs, as well as their overall impact on cancer biology. We focus on the latest research progress on how ncRNAs regulate the Notch pathway through transcriptional regulation, post-transcriptional modifications, and epigenetic mechanisms, and discuss how such interactions affect tumor microenvironment shaping, immune escape mechanisms, and treatment sensitivity. Additionally, this article deeply analyzes potential therapeutic strategies targeting the Notch-ncRNA axis, including its prospects for synergistic application with chemotherapy, radiotherapy, and immunotherapy. By integrating multi-cancer experimental data, we propose individualized diagnosis and treatment strategies based on tumor-specific Notch pathway and ncRNA expression patterns.

SOX11 and GLIS2: Novel Biomarkers for Understanding the Progression of Oral Leukoplakia

2025-06-20

Li Yi , Zhengyi Tang , Chijie Xiao +3 more | International Dental Journal

Regulation of matrix metalloproteinase-13 in cancer: Signaling pathways and non-coding RNAs in tumor progression and therapeutic targeting

2025-06-20

Deekshaa Chidambaram , Velan Subashini , Muthuvairaprasath Nanthanalaxmi +2 more | World Journal of Clinical Oncology

Matrix metalloproteinases (MMPs) are essential enzymes involved in extracellular matrix degradation and remodeling. Such processes are integral to normal tissue homeostasis and several pathological conditions such as cancer. Among these … Matrix metalloproteinases (MMPs) are essential enzymes involved in extracellular matrix degradation and remodeling. Such processes are integral to normal tissue homeostasis and several pathological conditions such as cancer. Among these MMPs, MMP-13 plays a key role in cancer progression, driving tumor invasion, metastasis, and angiogenesis. Despite significant advancements in understanding its biology, therapeutic targeting of MMP-13 remains challenging owing to its complex and multifaceted regulatory mechanisms. Recent studies have underscored the pivotal role of non-coding RNAs (ncRNAs), including long ncRNAs, microRNAs, and circular RNAs, in modulating MMP-13 expression. This review provides a comprehensive analysis of MMP-13 regulation by several signaling pathways, the influence of ncRNAs on these signaling pathways, and MMP-13 expression during cancer progression and metastasis. Furthermore, we explored the clinical relevance of ncRNA-mediated regulatory networks, highlighting their potential as diagnostic biomarkers and therapeutic targets in various cancers. By unraveling these regulatory mechanisms, this review offers valuable insights into innovative strategies for cancer diagnosis and treatment and emphasizes the translational significance of ncRNA-mediated MMP-13 regulation in oncology.

Comprehensive Bioinformatic Analysis of Epithelial-Mesenchymal Transition (EMT) Network-Related microRNAs As Candidate Signatures in Prostate Adenocarcinoma

2025-06-20

Gautam Prasad , Dilutpal Sharma , Anveshika Manoj +1 more | Cureus

Transcriptomic Analysis Reveals the Role of Long Non-Coding RNAs in Response to Drought Stress in Tibetan Hulless Barley

2025-06-20

Zitao Wang , Yue Fang , Qinyue Min +5 more | Biology

LncRNAs, a type of RNAs exceeding 200 nucleotides (nt) and lacking representative open reading frames (ORFs), have emerged as crucial regulatory molecules that modulate numerous growth and development processes in … LncRNAs, a type of RNAs exceeding 200 nucleotides (nt) and lacking representative open reading frames (ORFs), have emerged as crucial regulatory molecules that modulate numerous growth and development processes in plants. While substantial progress has been made in interpreting the functions and regulatory mechanisms of coding RNAs, the study of lncRNAs in Tibetan hulless barley remains incomplete. To elucidate the coordination of drought stress responses in Tibetan hulless barely by lncRNAs, we analyzed the previously published RNA-seq data from two cultivars of hulless barley, drought-tolerant (Z772) and drought-sensitive (Z013), subjected to varying durations of drought treatment (0, 1, and 5 h). Initially, we identified a total of 2877 lncRNAs through a strict pipeline, of which 2179 were co-expressed in both cultivars. Additionally, 331 and 367 lncRNAs showed cultivar-specific expression patterns in Z772 and Z013, respectively. Given the trans-regulatory functions of lncRNAs, we utilized WGCNA and uncovered 11 modules that were enriched in drought-responsive pathways. Within these modules, lncRNAs and neighboring PCGs were co-clustered in key control modules. The GO enrichment analysis of potential lncRNA-PCG pairs primarily involved processes related to the response to water deprivation, regulation of abiotic stress, and RNA metabolic processes. Notably, 12 high-confidence lncRNA-PCG pairs displayed concordant expression profiles, with some annotated as TFs. Two of these pairs were validated by qRT-PCR in the Tibetan hulless barley cultivar Kunlun 14. These findings suggested that lncRNAs may participate in regulatory networks involved in drought adaptation in Tibetan hulless barley, offering novel insights into the drought resistance mechanisms of Poaceae crops and potential targets for breeding drought-resistant varieties.

Integrative multi-omics and machine-learning approaches uncover a novel metabolic-related signature associated with cancer-associated fibroblasts in gastric cancer development

2025-06-20

Van Thi Ngoc Tram , Do Thi Minh Xuan , Doan Phuong Quy Nguyen +2 more | Computers in Biology and Medicine

Unveiling the Vital Role of ACTA2-AS1 in Human Cancers: Molecular Mechanisms and Clinical Applications

2025-06-19

Haodong He , Xiang Liu , Baoqin Pi +7 more | Anti-Cancer Agents in Medicinal Chemistry

Background: The smooth muscle α‑actin 2‑antisense 1 (ACTA2-AS1), also known as ZXF1, is an emerging cancer-associated long non-coding RNA (lncRNA) that has garnered significant attention in recent years. ACTA2-AS1 is … Background: The smooth muscle α‑actin 2‑antisense 1 (ACTA2-AS1), also known as ZXF1, is an emerging cancer-associated long non-coding RNA (lncRNA) that has garnered significant attention in recent years. ACTA2-AS1 is situated on human chromosome 10 at location 10q23.31, comprising five exons and a single transcript. The aberrant expression of ACTA2-AS1 has been noted in 10 malignant tumors, correlating significantly with unfavorable clinicopathological characteristics and poor patient prognosis. Objective: This review encapsulates recent progress in ACTA2-AS1 research, examining its expression profile, biological functions, molecular mechanisms, and anticipated influence on cancer diagnosis, treatment, and prognosis, emphasizing its potential as a novel therapeutic target based on lncRNA and its prognostic utility as a biomarker. Methods: Based on a comprehensive search of the PubMed database for the biological function of lncRNA ACTA2-AS1 in malignant tumors, the current research is systematically summarized and critically analyzed. Results: ACTA2-AS1 plays a complex role in various biological processes in tumor cells, encompassing proliferation, apoptosis, and cell cycle arrest. It also contributes to migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance. Mechanistically, ACTA2-AS1 influences oncogenic or tumor-suppressive effects via a complex regulatory network. It can adsorb specific 5 miRNAs as competitive endogenous RNAs (ceRNAs), thereby mitigating the suppression of downstream mRNA targets implicated in tumorigenesis (e.g., SOX7, KLF9, CXCL2, BCL2L11, etc.) and modulating their downstream signaling pathways (e.g., Wnt5a/PKC, SMAD3, mTOR, etc.), demonstrating a broad spectrum of dual roles in carcinogenesis and tumor suppression. Conclusion: ACTA2-AS1 is a promising biomarker and molecular target for the treatment of cancer.

Paeoniflorin mitigates iron overload-induced osteoarthritis by suppressing chondrocyte ferroptosis via the p53/SLC7A11/GPX4 pathway

2025-06-19

Boyu Wu , Zhiqiang Luo , Zehua Chen +4 more | International Immunopharmacology

X chromosome inactivation in mammals: general principles and species-specific considerations

2025-06-19

Charbel Alfeghaly , Claire Rougeulle | EMBO Reports

Abstract X chromosome inactivation (XCI) is a mammalian dosage compensation mechanism that ensures balanced expression of X-linked genes between males and females. Research using rodent models has led to major … Abstract X chromosome inactivation (XCI) is a mammalian dosage compensation mechanism that ensures balanced expression of X-linked genes between males and females. Research using rodent models has led to major discoveries regarding XCI mechanisms and dynamics, in addition to the molecular actors involved in this process, including the long noncoding RNA Xist and its protein partners. However, several features of XCI vary significantly across mammalian species, not only between marsupials and placental mammals, but also within the latter. This review discusses the fundamental aspects of XCI from an evolutionary perspective, highlighting both conserved features and species-specific variations across mammalian species.

Retraction: Up-regulation of long non-coding RNA SNHG20 promotes ovarian cancer progression via Wnt/β-catenin signaling

2025-06-01

| PubMed