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Bioinformatics Analysis Of The Functions Of Prostate Cancer Associated LincRNAs

Posted on:2015-01-06Degree:MasterType:Thesis
Country:ChinaCandidate:W R CuiFull Text:PDF
GTID:2254330428998508Subject:Systems Biology
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Long chain non-coding RNA (long non-coding RNA, lncRNA), is a class ofnucleotides greater than200in length and don’t have the ability of encoding proteins. Butso far the number of lncRNA understood clearly about its function is still minimal. Prostatecancer is a malignant tumor in the male reproductive system. What’s more, it is one of themost important male tumors causing death at present. With the progress of the cancertranscriptome research, more and more evidence showed that abnormal expression oflncRNA acts on the tumorigenesis. Therefore, the lncRNA research is of great significance.Based on the position in the genome, lncRNA can be divided into different sub-classes, andthe lncRNA located between genes are transcribed from the intergenic region, namely theLong intergenic non-coding RNAs(lincRNAs), which is the object this article explores. Weused a weighted gene co-expression network analysis (WGCNA) method to analysis theco-expression of the differentially expressed protein coding genes and lincRNA.We constructed a co-expression of scale-free network, made cluster analysis to obtainnine co-expression modules, performed aprincipal component analysis(PCA) on theexpression of matrix, applied the first principal componentas the eigengene of the entiremodule, and used eigengene expression values representing the overall expression of thewhole module. The Pearson’s correlationfor each gene and eigengene was calculated as themodule membership (kME). After obtaining the co-expression of prostate cancer module,we tested the significance if the modules related to prostate cancer and got three prostatecancer risk modules M1(black pcor=0.008219622); M3(cyan pcor=0.027801588); M5(magenta pcor=0.001489048). The cluster analysis showed that the eigengenes of moduleM3and module M5were close to each other. And the sub-network analysis on these three prostate cancer risk module(M1,M3,M5) and also found more lincRNAs in M3, M5module. In addition, the eigengenes of these two modules are rich in lincRNAs andregulates the same transcription factor Sp1, And these two modules of the miRNAsenrichment analysis results shows the miR-24and miR-330are Significant correlation(pvalue cutoff set as0.05) with the two module eigengenes, According to a report in theknown, the miR-24and miR-330are the biomarkers for Pca. In the research of genetic hubin the M3(“cyan”) network, there were seven lincRNAs (TCONSl200008237,TCONSl200022670, TCONSl200022611, linc-PXN-1, TCONSl200011130,TCONSl200001418, TCONSl200013175) in the prostate cancer risk moduleM3(“cyan”) playing an important role in the regulation of gene expression, and thereforethe biological function of lincRNA was validated in the network level. The eigengenes inthis module were put in the MetaCore GeneGO to do the gene enrichment analysis andit showed that transcriptional regulation, gene expression and other major biologicalprocesses contained the M3("cyan") module genes. All results confirming the regulatoryrole of lincRNA in prostate cancer. Through this series of bioinformatics methods, weillustrated how lincRNA co-expressed with protein-coding genes and exercised relatedfunctions. This topic can be used as guidance resources to provide new ideas and methodsfor the researchers to study lncRNA.
Keywords/Search Tags:Long intergenic noncoding RNAs (lincRNAs), Prostate cancer(PCa), RNA-Seq, Weighted gene co-expression network analysis(WGCNA), Enrichment analysis, Biological function
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