Effects of TRPV1 on biological behavior of hepatocellular carcinoma and prediction of possible mechanisms
Objective To clarify the expression of transient receptor potential vanilloid subfamily 1(TRPV1)in hepatocellular carcinoma(HCC)and its relationship with prognosis,and to explore its effect on the biological behavior of HCC cells.Methods The cancer genome atlas(TCGA),genotype-tissue expression(GTEx)and gene expression ominbus(GEO)databases were utilized to verify the ex-pression of TRPV1 in HCC and its relationship with prognosis.The effects of TRPV1 on the proliferation,migration,invasion,and cell cycle of HCC cells were detected by CCK-8 assay,scratch assay,Transwell assay,and flow cytometry.The expression of cyclin-dependent kinase 4(CDK4)and cyclin-dependent kinase 6(CDK6)was detected by Western blot,and the tumor proliferation ability was detected by sub-cutaneous tumor formation assay in nude mice.Finally,the TRPV1 co-expression network was constructed and analyzed for functional enrichment.Results The expression level of TRPV1 in HCC tissues was down-regulated in TCGA,GTEx,and GEO databases(P＜0.001)and was associated with a shorter over-all survival time of patients(P=0.032),with an area under the ROC curve of 0.91.Overexpression of TRPV1 suppressed the proliferation,migration,and invasion ability of HCC cells,blocked cell cycle pro-gression,and CDK4 and CDK6 protein expression levels decreased(both P＜0.05),and the opposite was true for knockdown of TRPV1(both P＜0.05).After stable overexpression of TRPV1,the subcutaneous tumor volume of nude mice was reduced(P=0.015),the mass of nude mice was reduced(P=0.033),and the positive expression level of Ki-67 protein was down-regulated(P=0.010).TRPV1 co-expressed genes were mainly involved in the processes of RNA splicing,cell cycle protein binding,and cell proliferation.Conclusions TRPV1 inhibited the proliferation,migration,and invasion of HCC cells and blocked cell cycle progression,which exerted an oncogenic role in HCC and provided a new direction for the prognostic analysis and treatment of HCC.
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