Non-coding RNAs in breast cancer
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ABSTRACT:
PROVIDER: EGAS00001003353 | EGA |
REPOSITORIES: EGA
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Project description:BACKGROUND: Transcription of large numbers of non-coding RNAs originating from intronic regions of human genes has been recently reported, but mechanisms governing their biosynthesis and biological functions are largely unknown. In this work, we evaluated the existence of a common mechanism of transcription regulation shared by protein-coding mRNAs and intronic RNAs by measuring the effect of androgen on the transcriptional profile of a prostate cancer cell line. RESULTS: Using a custom-built cDNA microarray enriched in intronic transcribed sequences, we found 39 intronic non-coding RNAs for which levels were significantly regulated by androgen exposure. Orientation-specific reverse transcription-PCR indicated that 10 of the 13 were transcribed in the antisense direction. These transcripts are long (0.5-5 kb), unspliced and apparently do not code for proteins. Interestingly, we found that the relative levels of androgen-regulated intronic transcripts could be correlated with the levels of the corresponding protein-coding gene (asGAS6 and asDNAJC3) or with the alternative usage of exons (asKDELR2 and asITGA6) in the corresponding protein-coding transcripts. Binding of the androgen receptor to a putative regulatory region upstream from asMYO5A, an androgen-regulated antisense intronic transcript, was confirmed by chromatin immunoprecipitation. CONCLUSIONS: Altogether, these results indicate that at least a fraction of naturally transcribed intronic non-coding RNAs may be regulated by common physiological signals such as hormones, and further corroborate the notion that the intronic complement of the transcriptome play functional roles in the human gene-expression program. Keywords: Time course study – effect of androgen on gene expression
2007-01-01 | GSE5345 | GEO
Project description:Angiotensin II (AngII) is a polypeptide hormone that plays a pivotal role in the regulation of blood pressure. In vascular smooth muscle cells (VSMCs), AngII signaling results in hypertrophy, proliferation, contraction, and migration, which ultimately promote atherosclerosis and hypertensive cardiovascular diseases. Recent studies have shown that fundamental biological processes such as cell proliferation and differentiation are mediated in part by the activities of long non-protein-coding RNAs (lncRNAs). In this study, we sought to identify lncRNAs that are involved in the response to AngII-signaling. Genome-wide analysis of de novo assembled transcripts from rat vascular smooth muscle cells (VSMCs) identified novel lncRNA as well as protein-coding transcripts which have not been previously annotated. The majority of the genomic loci from which these novel transcripts are transcribed are enriched for histone H3 lysine 4 trimethylation and histone H3 lysine 36 trimethylation, two chromatin modifications that are closely associated with actively transcribed regions, further supporting these as bona fide transcripts. Compared with previously annotated rat transcripts, these novel lncRNA transcripts, on average, are shorter in length and are less abundant, consistent with reports from mice and humans. Expression analyses of transcripts from control and AngII-stimulated VSMCs reveal that AngII signaling affects the abundance of both protein-coding transcripts as well as lncRNAs transcripts. Altogether, these data provide new insights into the global effects of AngII signaling and reveal potential novel therapeutic targets for treatment of AngII-associated cardiovascular diseases. RNA-sequencing of control and AngII (3hrs)-stimulated rVSMSCs. ChIP-sequencing of H3K4me3 and H3K36me3 in control and AngII (3hrs)-stimulated rVSMCs.
2013-06-30 | E-GEOD-38056 | biostudies-arrayexpress
Project description:Angiotensin II (AngII) is a polypeptide hormone that plays a pivotal role in the regulation of blood pressure. In vascular smooth muscle cells (VSMCs), AngII signaling results in hypertrophy, proliferation, contraction, and migration, which ultimately promote atherosclerosis and hypertensive cardiovascular diseases. Recent studies have shown that fundamental biological processes such as cell proliferation and differentiation are mediated in part by the activities of long non-protein-coding RNAs (lncRNAs). In this study, we sought to identify lncRNAs that are involved in the response to AngII-signaling. Genome-wide analysis of de novo assembled transcripts from rat vascular smooth muscle cells (VSMCs) identified novel lncRNA as well as protein-coding transcripts which have not been previously annotated. The majority of the genomic loci from which these novel transcripts are transcribed are enriched for histone H3 lysine 4 trimethylation and histone H3 lysine 36 trimethylation, two chromatin modifications that are closely associated with actively transcribed regions, further supporting these as bona fide transcripts. Compared with previously annotated rat transcripts, these novel lncRNA transcripts, on average, are shorter in length and are less abundant, consistent with reports from mice and humans. Expression analyses of transcripts from control and AngII-stimulated VSMCs reveal that AngII signaling affects the abundance of both protein-coding transcripts as well as lncRNAs transcripts. Altogether, these data provide new insights into the global effects of AngII signaling and reveal potential novel therapeutic targets for treatment of AngII-associated cardiovascular diseases.
2013-06-30 | GSE38056 | GEO
Project description:We describe a refined approach to identify new human RNA-protein interactions. In vitro transcribed labeled RNA is bound to ~9,400 human recombinant proteins spotted on protein microarrays. This approach identified 137 RNA-protein interactions for 10 human coding and non-coding RNAs, including an interaction between Staufen 1 protein and TP53 mRNA that promoted the latter’s stability. RNA hybridization to protein microarrays allows rapid identification of human RNA-protein interactions on a large scale. Sense and antisense strands for 10 RNA transcripts representing protein coding RNAs TP53, HRAS, MYC, BCL2 and non-coding sequences PWRN1, SOX2OT, OCC1, IGF2RNC, lncRBM26 and DLEU1 were in vitro transcribed, labeled with Cy5 and independently hybridized on human protein microarrays. The labeling process was optimized in order to achieve ~ 3 pmol dye per every microgram RNA with average efficacy of 1 dye molecule for approximately every 850 bp RNA to minimally influence RNA native structure and at the same time yield in signal intensities that were readily visualized.
2012-10-10 | E-GEOD-34794 | biostudies-arrayexpress
Project description:We describe a refined approach to identify new human RNA-protein interactions. In vitro transcribed labeled RNA is bound to ~9,400 human recombinant proteins spotted on protein microarrays. This approach identified 137 RNA-protein interactions for 10 human coding and non-coding RNAs, including an interaction between Staufen 1 protein and TP53 mRNA that promoted the latter’s stability. RNA hybridization to protein microarrays allows rapid identification of human RNA-protein interactions on a large scale.
2012-10-10 | GSE34794 | GEO
Project description:We employed whole-genome RNA-sequencing to profile mRNAs and both annotated and novel long noncoding RNAs (lncRNAs) in human naive, central memory, and effector memory CD4+ T cells. Loci transcribing both lineage-specific annotated and novel lncRNA are adjacent to lineage-specific protein-coding genes in the genome. Lineage-specific novel lncRNA loci are transcribed from lineage-specific typical- and supertranscriptional enhancers and are not multiexonic, thus are more similar to enhancer RNAs. Novel enhancer-associated lncRNAs transcribed from the IFNG locus bind the transcription factor NF-κB and enhance binding of NF-κB to the IFNG genomic locus. Depletion of the annotated lncRNA, IFNG-AS1, or one IFNG enhancer-associated lncRNA abrogates IFNG expression by memory T cells, indicating these lncRNAs have biologic function.
2017-06-11 | GSE85294 | GEO
Project description:Recent genome-wide studies revealed that only 2% of the human genome encodes for mRNAs that are translated into proteins while as much as 80% of the genome can be transcribed. Of these non-coding transcripts, long non-coding RNAs (lncRNAs) represent the largest and most diverse class, comprising almost 16,000 currently annotated transcripts in human and 10,000 in mouse. Here, we investigated the role of lncRNAs in mammary tumors by performing RNA-Seq on tumor sections and organoids derived from MMTV-PyMT and MMTV-Neu-NDL mice. We identified several hundred long non-coding transcripts that were over-expressed compared to the normal mammary epithelium. Among these potentially oncogenic lncRNAs we prioritized a subset as Mammary Tumor Associated RNAs (MaTARs) and determined their human counterparts, hMaTARs. To functionally validate the role of MaTARs, we performed antisense knockdown and observed reduced cell proliferation, invasion and/or organoid branching in a cancer-specific context. Assessing the expression of hMaTARs in human breast tumors revealed that 19 hMaTARs are significantly up-regulated and many of these correlate with breast cancer subtype and/or hormone receptor status, indicating potential clinical relevance.
2016-09-28 | GSE72823 | GEO
Project description:Organismal growth and development rely on RNA Polymerase II (RNAPII) synthesizing the appropriate repertoire of messenger RNAs (mRNAs) from protein-coding genes. Productive elongation of full-length transcripts is essential for mRNA function, however what determines whether an engaged RNAPII molecule will terminate prematurely or transcribe processively remains poorly understood. Notably, despite a common process for transcription initiation across RNAPII-synthesized RNAs1, RNAPII is highly susceptible to termination when transcribing non-coding RNAs such as upstream antisense RNAs (uaRNAs) and enhancers RNAs (eRNAs)2, suggesting that differences arise during RNAPII elongation. To investigate the impact of transcribed sequence on elongation potential, we developed a method to screen the effects of thousands of INtegrated Sequences on Expression of RNA and Translation using high-throughput sequencing (INSERT-seq). We found that higher AT content in uaRNAs and eRNAs, rather than specific sequence motifs, underlies the propensity for RNAPII termination on these transcripts. Further, we demonstrate that 5’ splice sites exert both splicing-dependent and autonomous, splicing-independent stimulation of processive transcription, even in the absence of polyadenylation signals. Together, our results reveal a potent role for transcribed sequence in dictating gene output at mRNA and non-coding RNA loci, and demonstrate the power of INSERT-seq towards illuminating these contributions.
2022-04-06 | GSE178230 | GEO
Project description:Erythropoiesis is regulated at multiple levels to ensure the proper generation of mature red cells under multiple physiological conditions. To probe the contribution of long non-coding RNAs (lncRNAs) to this process, we examined >1 billion RNA-Seq reads of polyadenylated and nonpolyadenylated RNA from differentiating mouse fetal liver red blood cells, and identified 655 lncRNA genes including not only intergenic, antisense and intronic but also pseudogene and enhancer loci. Over 100 of these genes are previously unrecognized and highly erythroidspecific. By integrating genome-wide surveys of chromatin states, transcription factor occupancy, and tissue expression patterns, we identify multiple lncRNAs that are dynamically expressed during erythropoiesis, show epigenetic regulation and are targeted by key erythroid transcription factors GATA1, TAL1 or KLF1. We focus on 12 such candidates and find that they are nuclear-localized and exhibit complex developmental expression patterns. Depleting them severely impaired erythrocyte maturation, inhibiting cell size reduction and subsequent enucleation. One of them, alncRNA-EC7, is transcribed from an enhancer and is specifically needed for activation of the neighboring gene encoding BAND3. Our study provides an annotated catalog of erythroid lncRNAs, readily available through an online resource, and shows that diverse types of lncRNAs participate in the regulatory circuitry underlying erythropoiesis. one Ter119- total RNA, one Ter119+ total RNA, one Ter119+ poly(A)+ RNA, one Ter119+ poly(A)- RNA, all are Hi-seq Ilumina data
2013-11-07 | E-GEOD-52126 | biostudies-arrayexpress
Project description:Genome-wide association studies have identified numerous genetic variants conferring autoimmune disease risk. Most of these genetic variants lie outside protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also differentially expressed in autoimmune disease but their regulation is also unclear. The majority of the human genome is transcribed yet its biologic significance is incompletely understood. We performed whole genome RNA-sequencing [RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs [lncRNAs] in leukocytes from subjects with autoimmune disease and identified annotated and novel lncRNAs differentially expressed across multiple disorders. We found that loci transcribing novel lncRNAs were not randomly distributed across the genome but co-localized with leukocyte transcriptional enhancers, especially super-enhancers, and near genetic variants associated with autoimmune disease risk. We propose that alterations in enhancer function, including lncRNA expression, produced by genetics and environment, change cellular phenotypes contributing to disease risk and pathogenesis and represent attractive therapeutic targets.
2017-04-11 | GSE92472 | GEO