Dataset Information

Discovery and characterization of long intergenic non-coding RNAs (lincRNA) module biomarkers in prostate cancer: an integrative analysis of RNA-Seq data.

ABSTRACT: Prostate cancer (PCa) is a leading cause of cancer-related death of men worldwide. There is an urgent need to develop novel biomarkers for PCa prognosis and diagnosis in the post prostate-specific antigen era. Long intergenic noncoding RNAs (lincRNAs) play essential roles in many physiological processes and can serve as alternative biomarkers for prostate cancer, but there has been no systematic investigation of lincRNAs in PCa yet.Nine lincRNA co-expression modules were identified from PCa RNA-Seq data. The association between the principle component of each module and the PCa phenotype was examined by calculating the Pearson's correlation coefficients. Three modules (M1, M3, and M5) were found associated with PCa. Two modules (M3 and M5) were significantly enriched with lincRNAs, and one of them, M3, may be used as a lincRNA module-biomarker for PCa diagnosis. This module includes seven essential lincRNAs: TCONS_l2_00001418, TCONS_l2_00008237, TCONS_l2_00011130, TCONS_l2_00013175, TCONS_l2_00022611, TCONS_l2_00022670 and linc-PXN-1. The clustering analysis and microRNA enrichment analysis further confirmed our findings.The correlation between lincRNAs and protein-coding genes is helpful for further exploration of functional mechanisms of lincRNAs in PCa. This study provides some important insights into the roles of lincRNAs in PCa and suggests a few lincRNAs as candidate biomarkers for PCa diagnosis and prognosis.

SUBMITTER: Cui W

PROVIDER: S-EPMC4474418 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Discovery and characterization of long intergenic non-coding RNAs (lincRNA) module biomarkers in prostate cancer: an integrative analysis of RNA-Seq data.

Cui Weirong W Qian Yulan Y Zhou Xiaoke X Lin Yuxin Y Jiang Junfeng J Chen Jiajia J Zhao Zhongming Z Shen Bairong B

BMC genomics 20150611

<h4>Background</h4>Prostate cancer (PCa) is a leading cause of cancer-related death of men worldwide. There is an urgent need to develop novel biomarkers for PCa prognosis and diagnosis in the post prostate-specific antigen era. Long intergenic noncoding RNAs (lincRNAs) play essential roles in many physiological processes and can serve as alternative biomarkers for prostate cancer, but there has been no systematic investigation of lincRNAs in PCa yet.<h4>Results</h4>Nine lincRNA co-expression mo ...[more]

PMID: 26100580

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Project description:Recently, large numbers of normal human tissues have been profiled for non-coding RNAs and more than fourteen thousand long intergenic non-coding RNAs (lincRNAs) are found expressed in normal human tissues. The functional roles of these normal lincRNAs (nlincRNAs) in the regulation of protein coding genes in normal and disease biology are yet to be established. Here, we have profiled two RNA-seq datasets including cancer and matched non-neoplastic tissues from 12 individuals from diverse demography for both coding genes and nlincRNAs. We find 130 nlincRNAs significantly regulated in cancer, with 127 regulated in the same direction in the two datasets. Interestingly, according to Illumina Body Map, significant numbers of these nlincRNAs display baseline null expression in normal prostate tissues but are specific to other tissues such as thyroid, kidney, liver and testis. A number of the regulated nlincRNAs share loci with coding genes, which are either co-regulated or oppositely regulated in all cancer samples studied here. For example, in all cancer samples i) the nlincRNA, TCONS_00029157, and a neighboring tumor suppressor factor, SIK1, are both down regulated; ii) several thyroid-specific nlincRNAs in the neighborhood of the thyroid-specific gene TPO, are both up-regulated; and iii) the TCONS_00010581, an isoform of HEIH, is down-regulated while the neighboring EZH2 gene is up-regulated in cancer. Several nlincRNAs from a prostate cancer associated chromosomal locus, 8q24, are up-regulated in cancer along with other known prostate cancer associated genes including PCAT-1, PVT1, and PCAT-92. We observe that there is significant bias towards up-regulation of nlincRNAs with as high as 118 out of 127 up-regulated in cancer, even though regulation of coding genes is skewed towards down-regulation. Considering that all reported cancer associated lincRNAs (clincRNAs) are biased towards up-regulation, we conclude that this bias may be functionally relevant.

Project description:BACKGROUND:Long non-coding RNAs (lncRNAs) are key regulators of diverse cellular processes. Although a number of studies have reported the identification of bovine lncRNAs across many tissues, very little is known about the identity and characteristics of lncRNAs in bovine oocytes. METHODS:A bovine oocyte cDNA library was constructed and sequenced using the Illumina HiSeq 2000 sequencing system. The oocyte transcriptome was constructed using the ab initio assembly software Scripture and Cufflinks. The assembled transcripts were categorized to identify the novel intergenic transcripts, and the coding potential of these novel transcripts was assessed using CPAT and PhyloCSF. The resulting candidate long intergenic non-coding RNAs (lincRNAs) transcripts were further evaluated to determine if any of them contain any known protein coding domains in the Pfam database. RT-PCR was used to analyze the expression of oocyte-expressed lincRNAs in various bovine tissues. RESULTS:A total of 85 million raw reads were generated from sequencing of the bovine oocyte library. Transcriptome reconstruction resulted in the assembly of a total of 42,396 transcripts from 37,678 genomic loci. Analysis of the assembled transcripts using the step-wide pipeline resulted in the identification of 1535 oocyte lincRNAs corresponding to 1183 putative non-coding genes. A comparison of the oocyte lincRNAs with the lncRNAs reported in other bovine tissues indicated that 970 of the 1535 oocyte lincRNAs appear to be unique to bovine oocytes. RT-PCR analysis of 5 selected lincRNAs showed either specific or predominant expression of 4 lincRNAs in the fetal ovary. Functional prediction of the oocyte-expressed lincRNAs suggested their involvement in oogenesis through regulating their neighboring protein-coding genes. CONCLUSIONS:This study provides a starting point for future research aimed at understanding the roles of lncRNAs in controlling oocyte development and early embryogenesis in cattle.

Dataset Information

Discovery and characterization of long intergenic non-coding RNAs (lincRNA) module biomarkers in prostate cancer: an integrative analysis of RNA-Seq data.

Publications

Discovery and characterization of long intergenic non-coding RNAs (lincRNA) module biomarkers in prostate cancer: an integrative analysis of RNA-Seq data.

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