PAQR4在肝细胞癌中的表达及其对HepG2细胞生物学特性的影响

Expression of PAQR4 in hepatocellular carcinoma and its effect on the biological characteristics of HepG2 cells

目的探究PAQR4在肝细胞癌(HCC)中的表达、预后及其对HepG2细胞的增殖、侵袭、迁移和凋亡的影响。方法利用TCGA数据库中HCC的数据分析PAQR4 mRNA在HCC组织中的表达及对患者的预后意义。构建pcDNA3.1-PAQR4实验组与pcDNA3.1-vector对照组的HepG2细胞株。采用CCK-8法检测过表达PAQR4对HepG2细胞增殖的影响。通过细胞划痕实验和Transwell侵袭实验分别检测过表达PAQR4对HepG2细胞迁移和侵袭能力的影响。利用PI和Annexin V双染实验观察过表达PAQR4对HepG2细胞凋亡的影响。结果TCGA数据库数据分析结果显示PAQR4 mRNA在HCC组织中的表达高于癌旁组织(P<0.05),且PAQR4 mRNA高表达组HCC患者的总体生存率低于低表达组(P=0.012)。单因素回归分析显示PAQR4 mRNA表达水平(HR:1.104,95%CI:1.051~1.160,P<0.001)、T分期(HR:1.816,95%CI:1.442~2.287,P<0.001)、M分期(HR:3.924,95%CI:1.230~12.519,P=0.021)、病理分期(HR:1.879,95%CI:1.466~2.408,P<0.001)对HCC患者的预后存在显著影响。多因素回归分析显示PAQR4 mRNA表达水平(HR:1.396,95%CI:1.081~1.804,P=0.011)是HCC患者预后的独立危险因素。CCK-8实验、划痕实验和Transwell侵袭实验结果表明,与对照组相比,实验组中HepG2细胞的增殖、迁移、侵袭能力均明显得到促进(P<0.05)。细胞凋亡实验结果显示过表达PAQR4可以抑制HepG2细胞凋亡(P<0.05)。结论PAQR4在HCC组织中高表达且与预后相关,过表达PAQR4促进HepG2细胞的增殖、侵袭、迁移并抑制HepG2细胞的凋亡。PAQR4有可能成为HCC诊断和预后的新标志物。

Objective To investigate the expression and prognosis of(progestin and adipoQ receptor family member 4,PAQR4)in hepatocellular carcinoma(HCC)and its effect on the proliferation,invasion,migration and apoptosis of HepG2 cells.Methods The HCC data in the cancer genome atlas(TCGA)database was used to analyze the expression of PAQR4 mRNA in the tissues of HCC and its prognostic significance.HepG2 cell lines of pcDNA3.1-PAQR4 experimental group and pcDNA3.1-vector control group were established.CCK-8 assay was used to detect the effect of overexpression PAQR4 on the proliferation of HepG2 cells.The scratch assay and Transwell assay were used to detect the effects of PAQR4 overexpression on the migration and invasion of HepG2 cells.PI and Annexin V double staining experiment was used to observe the effect of PAQR4 overexpression on HepG2 cell apoptosis.Results TCGA database data analysis results showed that the expression of PAQR4 mRNA in HCC tissues was higher than that in adjacent tissues(P<0.05),and the overall survival rate of HCC patients with PAQR4 mRNA high expression group was lower than that of low expression group(P=0.012).Univariate regression analysis showed that PAQR4 mRNA expression level(HR:1.104,95%CI:1.051-1.160,P<0.001),T stage(HR:1.816,95%CI:1.442-2.287,P<0.001),M stage(HR:3.924,95%CI:1.230-12.519,P=0.021),pathological staging(HR:1.879,95%CI:1.466-2.408,P<0.001)had a significant impact on the prognosis of HCC patients.Multivariate regression analysis showed that PAQR4 mRNA expression level(HR:1.396,95%CI:1.081-1.804,P=0.011)was an independent risk factor of the prognosis of HCC patients.The results of CCK-8 assay,scratch assay and Transwell assay showed that the proliferation,migration,invasion and invasion ability of HepG2 cells in the experimental group were significantly improved compared with the control group(P<0.05).Overexpression PAQR4 could inhibit HepG2 cell apoptosis(P<0.05).Conclusion PAQR4 is significantly up-regulated in HCC tissue and is related to the prognosis of the patients.Overexpression PAQR4 promotes the proliferation,invasion and migration of HepG2 cells,and inhibits HepG2 cells apoptosis.PAQR4 maybe a new marker for the diagnosis and prognosis of HCC.