The Expression Of PVT1 In HCC And The Primary Exploration Of Its Bioinformatic Functions

BackgroundLiver cancer ranks as one of the top ten malignant tumors,with the third of mortality in China.Its incidence and mortality rates showed an upward trend,although a variety of methods have been widely used in clinical therapy,including resection、liver transplantation、 ablation and chemotherapy.With the wide spread of bioinformatics,a large number of researchers have focused on the molecular therapy,especially long non-coding RNA(lnc RNA)and micro RNA(mi RNA).Materials and Methods1.The Cancer Genome Atlas(TCGA)data base was performed to calculate the aberrant expression of PVT1 in HCC tissues and normal liver tissues.It was also used to analyze the relationship of PVT1 expression and HCC clinicalpathological features.Besides,we also compared the expression level of PVT1 in different HCC cell lines and normal liver cells.2.SMMC-7721 HCC cell lines was transfected with lentivirus to knockdown PVT1 in order to detect the gene expression profile and mi RNA expression profile.3.We predicted the targets of mi R-302b-5p in silico and conducted Gene Ontology and Pathway analyses.In addition,we further concluded the genes regulated both by PVT1 and mi R-302b-5p.Results1.The results of TCGA data showed that PVT1 expression level was much higher in HCC tissues than that in normal liver tissues.And PVT1 was upregulated in male yellow race patients in comparison with female and white/black race patients.What is more,the upregulation of PVT1 was associated with micro-vascular invasion and pathological grade.The receiver operating characteristic curve(ROC)showed that different expression of PVT1 was in favor of diagnosis of patients divided into different groups,including gender and pathological grade.What is more,race and pathological grade could be function as independent risk factors in evaluating the prognosis of HCC patients.2.The outcome of gene array and mi RNA array.The outcome of gene array showed that 195 genes were upregulated after knockdown of PVT1,and these genes were involved twenty nine pathways,including Antigen processing and presentation 、 HTLV-I infection 、 Allograft rejection 、 Cell adhesion molecules 、 Natural killer cell mediated cytotoxicity.Besides,sixty genes expression was decreased and they were in relation to seventeen signal pathway: Drug metabolism-other enzymes、Drug metabolism-cytochrome P450、Chemical carcinogenesis 、HTLV-I infection.In addition,two mi RNAs(mi R-302b-5p and mi R-5191)were increased with knockdown of PVT1.3.We found 416 target genes associated with mi R-302b-5p in silico,and the GO analysis demonstrated that mi R-302b-5p might regulate targets at the transcriptional level.The pathway analysis verified that mi R-302b-5p targets mainly regulared the following pathways: Cell cycle、Erb B signaling pathway、MAPK signaling pathway 、 Axon guidance 、 TGF-beta signaling pathway 、Endocytosi.Besides,DYRK2 、 MECP2 、 KBTBD8 might be target genes regulated both by PVT1 and mi R-302b-5p.ConclusionsThe results of TCGA data demonstrated that the different expression of PVT1 was positively associated with the vascular invasion and pathological grade,and the high expression level of PVT1 could predict poor prognosis in patients with HCC.What is more,the outcome of gene expression profile and mi RNA expression profile showed that PVT1 might modulate the expression of DYRK2、MECP2 by regulating mi R-302b-5p,which might affect the progression of HCC.