细胞周期蛋白A2在肝细胞癌中的表达及其意义

Expression of cyclin A2 in hepatocellular carcinoma and its significance

目的:探讨细胞周期蛋白A2(CCNA2)在肝细胞癌(HCC)中的表达及其意义。方法:从TCGA、GEO、GETx数据库获得测序数据,通过STATA 15.0进行meta分析评估HCC患者肿瘤组织中CCNA2 mRNA的表达水平;通过数据库GEPIA绘制CCNA2在HCC中的生存曲线,探究CCNA2对HCC预后的影响。在HCC细胞系(Huh7和SK-Hep1)沉默CCNA2(shCCNA2组),并设置空载体对照组(shNC组),通过细胞功能学实验检测沉默CCNA2对HCC细胞增殖、迁移与侵袭、细胞周期和细胞凋亡中的影响。通过在鸡胚绒毛尿囊膜构建HCC细胞移植瘤模型,观察并分离瘤体,检测CCNA2在体内对HCC生长的影响。结果:CCNA2在HCC患者肿瘤组织中m RNA水平显著高于非癌肝组织(SMD=1.65,95%CI:1.46~1.85,I2=89%)。CCNA2高表达与肝癌患者的不良预后呈负相关关系。与shNC组相比,shCCNA2组细胞增殖、迁移和侵袭能力降低(P<0.05)。shCCNA2组Huh7和SK-Hep1细胞的G0/G1期、S期、G2/M期占比发生改变(P<0.05)。鸡胚绒毛尿囊膜移植成瘤实验中,与shNC组比较,shCCNA2组肿瘤体积明显减小(P<0.05)。结论:CCNA2可能通过影响HCC细胞的增殖、迁移和侵袭能力,抑制HCC的进展和转移,其有望成为HCC治疗靶点。

Objective:To explore the expression and significance of cyclin A2(CCNA2)in hepatocellular carcinoma(HCC).Methods:Sequencing data were obtained from TCGA,GEO and GETx databases,and meta-analysis was performed by STATA 15.0 to assess CCNA2 mRNA expression level in the tumor tissues of HCC patients;the survival curve of CCNA2 in HCC was plotted by database gene expression profiling interactive analysis(GEPIA)to explore the effect of CCNA2 on the prognosis of HCC.The silencing CCNA2(shCCNA2)gene was silenced in HCC cell lines(Huh7 and SK-Hep1)and the empty vector control group(shNC group)was set up.The effect of shCCNA2 on HCC cell proliferation,migration,invasion,cell cycle and apoptosis were detected by cell functional experiments.The tumor model of HCC cell transplantation was constructed in chicken embryo chorioallantoic membrane,and the tumor was observed and isolated to detect the effect of CCNA2 on HCC growth in vivo.Results:CCNA2 mRNA level was significantly higher in the tumor tissues of HCC patients than that in noncancerous liver tissues(SMD=1.65;95%CI:1.46-1.85;I2=89%);a high level of CCNA2 expression was negatively correlated with a poor prognosis of hepatocellular carcinoma patients.Compared with shNC group,cell proliferation,migration and invasion in shCCNA2 group decreased(P<0.05);shCCNA2 altered the percentage of G0/G1 phase,S phase and G2/M phase in Huh7 and SK-Hep1 cells(P<0.05).In the tumor formation experiment of chicken embryo chorioallantoic membrane transplantation,the tumor volume in the shCCNA2 group was significantly reduced compared with the shNC group(P<0.05).Conclusion:CCNA2 may inhibit the progression and metastasis of HCC by affecting the proliferation,migration and invasion of HCC cells.It is promising to become a therapeutic target for HCC.