The Landscape of Antisense Gene Expression in Human Cancers
Ontology highlight
ABSTRACT: High throughput RNA Sequencing has revealed that the human genome is widely transcribed. However, the extent of natural antisense transcription, the molecular mechanisms by which natural antisense transcripts (NATs) might affect their cognate sense genes, and the role of NATs in cancer are less well understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) on a cohort of 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. Our results reveal that greater than 60% of annotated transcripts have measureable antisense expression and the expression of sense and antisense transcript pairs is in general positively correlated. Furthermore, by studying the expression of sense/antisense pairs across tissues we identify lineage-specific, ubiquitous and cancer-specific antisense loci. Our results raise the possibility that NATs participate in the regulation of well-known tumor suppressors and oncogenes. Finally, this study provides a catalogue of cancer related genes with significant antisense transcription (oncoNAT). This resource will allow researchers to investigate the molecular mechanisms of sense/antisense regulation and further advance our understanding of their role in cancer.
SECONDARY ACCESSION(S): PRJNA287192PRJNA287193
REPOSITORIES: dbGaP
Dataset's files
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:High throughput RNA sequencing has revealed pervasive transcription of human genome than previously anticipated. However, the extent of natural antisense transcripts (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) data from 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigations of sense/antisense pair expression across tissue types revealed lineage-specific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide oncoNAT, a catalog of cancer related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using oncoNAT we identified several functional NATs, including NKX2-1-AS that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs regulation of tumor suppressors and oncogenes in cancer biology. Strand-specific RNA sequencing data (ssRNASeq) of cancer and benign samples. SRP048484 (PRJNA262128).
2015-05-28 | E-GEOD-66727 | biostudies-arrayexpress
Project description:High throughput RNA sequencing has revealed pervasive transcription of human genome than previously anticipated. However, the extent of natural antisense transcripts (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) data from 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigations of sense/antisense pair expression across tissue types revealed lineage-specific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide oncoNAT, a catalog of cancer related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using oncoNAT we identified several functional NATs, including NKX2-1-AS that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs regulation of tumor suppressors and oncogenes in cancer biology. Strand-specific RNA sequencing data (ssRNASeq) of cancer and benign samples. SRP050021 (PRJNA267614). Processed data files linked to SuperSeries record.
2015-05-28 | E-GEOD-66728 | biostudies-arrayexpress
Project description:High throughput RNA sequencing has revealed pervasive transcription of human genome than previously anticipated. However, the extent of natural antisense transcripts (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) data from 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigations of sense/antisense pair expression across tissue types revealed lineage-specific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide oncoNAT, a catalog of cancer related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using oncoNAT we identified several functional NATs, including NKX2-1-AS that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs regulation of tumor suppressors and oncogenes in cancer biology.
2015-05-28 | GSE66728 | GEO
Project description:High throughput RNA sequencing has revealed pervasive transcription of human genome than previously anticipated. However, the extent of natural antisense transcripts (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) data from 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigations of sense/antisense pair expression across tissue types revealed lineage-specific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide oncoNAT, a catalog of cancer related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using oncoNAT we identified several functional NATs, including NKX2-1-AS that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs regulation of tumor suppressors and oncogenes in cancer biology.
2015-05-28 | GSE66727 | GEO
Project description:<p>During rheumatoid arthritis (RA), TNF activates fibroblast-like synoviocytes (FLS) inducing in a temporal order a constellation of genes, which perpetuate synovial inflammation. Although the molecular mechanisms regulating TNF-induced transcription are well characterized, little is known about the impact of mRNA stability on gene expression and the impact of TNF on decay rates of mRNA transcripts in FLS. To address these issues we performed RNA sequencing and genome-wide analysis of the mRNA stabilome in RA FLS. We found that TNF induces a biphasic gene expression program: initially, the inducible transcriptome consists primarily of unstable transcripts but progressively switches and becomes dominated by very stable transcripts. This temporal switch is due to: a) TNF-induced prolonged stabilization of previously unstable transcripts that enables progressive transcript accumulation over days and b) sustained expression and late induction of very stable transcripts. TNF- induced mRNA stabilization in RA FLS occurs during the late phase of TNF response, is MAPK-dependent, and involves several genes with pathogenic potential such as IL6, CXCL1, CXCL3, CXCL8/IL8, CCL2, and PTGS2. These results provide the first insights into genome-wide regulation of mRNA stability in RA FLS and highlight the potential contribution of dynamic regulation of the mRNA stabilome by TNF to chronic synovitis.</p>
| phs001371 | dbGaP
Project description:In the cytoplasm, small RNAs can control mammalian translation by regulating the stability of mRNA. In the nucleus, small RNAs can also control transcription and splicing. The mechanisms for RNA-mediated nuclear regulation are not understood and remain controversial, hindering the effective application of nuclear RNAi and blinding investigation of its natural regulatory roles. Here we reveal that the human GW182 paralogs TNRC6A/B/C are central organizing factors critical to RNA-mediated transcriptional activation. Mass spectrometry of purified nuclear lysates followed by experimental validation demonstrates that TNRC6A interacts with proteins involved in protein degradation, RNAi, the CCR4-NOT complex, the mediator complex, and histone modifying complexes. Functional analysis implicates TNRC6A, NAT10, MED14, and WDR5 in RNA-mediated transcriptional activation. These findings describe protein complexes capable of bridging RNA-mediated sequence-specific recognition of noncoding RNA transcripts with the regulation of gene transcription.
2017-07-07 | MSV000081227 | MassIVE
Project description:Background: Recent studies have identified thousands of sense-antisense gene pairs across different genomes by computational mapping of cDNA sequences. These studies have shown that approximately 25% of all transcriptional units in the human and mouse genomes are involved in cis-sense-antisense pairs. However, the number of known sense-antisense pairs remains limited because currently available cDNA sequences represent only a fraction of the total number of transcripts comprising the transcriptome of each cell type. Results: To discover novel antisense transcripts encoded in the antisense strand of important genes, such as cancer-related genes, we conducted expression analyses of antisense transcripts using our custom microarray platform along with 2376 probes designed specifically to detect the potential antisense transcripts of 501 well-known genes suitable for cancer research. Using colon cancer tissue and normal tissue surrounding the cancer tissue obtained from 6 patients, we found that antisense transcripts without poly(A) tails are expressed from approximately 80% of these well-known genes. This observation is consistent with our previous finding that many antisense transcripts expressed in a cell are poly(A)-. We also identified 101 and 71 antisense probes displaying a high level of expression specifically in normal and cancer tissues respectively. Some of these probes showed characteristic expression patterns which are anti-correlated with the expression patterns of the sense genes. Conclusion: Our microarray analysis identified novel antisense transcripts with expression profiles specific to cancer tissue, some of which might play a role in the regulatory networks underlying oncogenesis and thus are potential targets for further experimental validation. 501 probes targeting well-known genes suitable for cancer researches were designed. Additionally 2,376 probes targeting putative transcription units on the antisense strand of these genes were designed. Samples were obtained from colon cancer tissues and normal tissues surrounding cancer tissues of six patients.
2011-03-01 | E-GEOD-14397 | biostudies-arrayexpress
Project description:Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.
| EGAS00001002865 | EGA
Project description:Background: Recent studies have demonstrated that antisense transcription is pervasive in budding yeasts and is conserved between Saccharomyces cerevisiae and S. paradoxus. While studies have examined antisense transcripts of S. cerevisiae for inverse transcription in stationary phase and stress conditions, there is a lack of comprehensive analysis of the conditional specific evolutionary characteristics of antisense transcription between yeasts. Here we attempt to decipher the evolutionary relationship of antisense transcription of S. cerevisiae and S. paradoxus cultured in mid log, early stationary phase, and heat shock conditions. Results: Massively parallel sequencing of sequence strand-specific cDNA library was performed from RNA isolated from S. cerevisiae and S. paradoxus cells at mid log, stationary phase and heat shock conditions. We performed this analysis using a stringent set of sense ORF transcripts and non-coding antisense transcripts that were expressed in all the three conditions, as well as in both species. We found the divergence of the condition specific anti-sense transcription levels is higher than that in condition specific sense transcription levels, suggesting that antisense transcription played a potential role in adapting to different conditions. Furthermore, 43% of sense-antisense pairs demonstrated inverse transcription in either stationary phase or heat shock conditions relative to the mid log conditions. In addition, a large part of sense-antisense pairs (67%), which demonstrated inverse transcription, were highly conserved between the two species. Our results were also concordant with known functional analyses from previous studies and with the evidence from mechanistic experiments of role of individual genes. Conclusions: This study provides a comprehensive picture of the role of antisense transcription mediating sense transcription in different conditions across yeast species. We can conclude from our findings that antisense regulation could act like an on-off switch on sense regulation in different conditions. Transcriptomes of two yeast species under mid-log phase, early stationary phase, and after heat shock treatment were generated by Illumina HiSeq 2000 paired-end sequencing
2014-06-09 | E-GEOD-58319 | biostudies-arrayexpress
Project description:Widely reported discrepancies between metabolic flux and transcripts or enzyme levels in bacterial metabolism imply complex regulation mechanisms need to be considered, especially in new bacterial platforms for bioremediation and bioproduction. Comamonas testosteroni strains, which metabolize various natural and xenobiotic aromatic compounds, represent such platforms whose metabolic regulations are still unknown. Here, we identify analogous multi-level regulation mechanisms in the metabolism of two lignin-related (4-hydroxybenzoate and vanillate) and one plastic-related (terephthalate) aromatic compounds in C. testosteroni KF-1, a wastewater isolate. Transcription-level regulation controlled initial catabolism and cleavage of the compounds, but subsequent carbon fluxes in central carbon metabolism are governed by metabolite-level thermodynamic regulation. Quantitative 13C-fingerprinting of tricarboxylic acid cycle and cataplerotic reactions elucidate key carbon routing that is not evident from enzyme abundance changes. Therefore, as-needed transcriptional activation of aromatic catabolism is coupled with metabolic fine-tuning of central metabolism, thus delineating pathway candidates for different metabolic manipulations.
2022-11-21 | MTBLS3947 | MetaboLights