Project description:We characterized the expression patterns of sense-antisense transcripts, based on available cDNA sequences, in colon (colorectal) cancer tissues and in normal tissues surrounding the cancer tissues. Although expression balances (ratios) of most of sense and antisense transcript pairs did not change between patients or between normal and cancer tissues, we found 68 sense-antisense transcripts whose expression balances were altered specifically in colon cancer tissues.
Project description:We characterized the expression patterns of sense-antisense transcripts, based on available cDNA sequences, in colon (colorectal) cancer tissues and in normal tissues surrounding the cancer tissues. Although expression balances (ratios) of most of sense and antisense transcript pairs did not change between patients or between normal and cancer tissues, we found 68 sense-antisense transcripts whose expression balances were altered specifically in colon cancer tissues. We conducted DNA microarray analyses by using the same set of probes designed for 2621 sense-antisense pairs to detect transcripts expressed in colon cancer tissues. These probes comprise 2358 pairs for the detection of protein-coding transcripts only, 250 pairs for the detection of protein-coding transcripts paired with non-protein-coding transcripts, and 13 pairs for the detection of non-protein-coding transcripts only.
Project description:<p>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.</p>
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.
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.
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.
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.
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).