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

  • 摘要: 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mRNA 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。

     

    Abstract: Objective:To explore the expression and significance of cyclin A2 (CCNA2) in hepatocellular carci-noma(HCC).Methods:Sequencing data were obtained from TCGA, GEO and GETx databases, and meta-analy-sis 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(GE-PIA) to explore the effect of CCNA2 on the prognosis of HCC.The silencing CCNA2 (shCCNA2) gene was si-lenced 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 chorio-allantoic membrane, and the tumor was observed and isolated to detect the effect of CCNA2 on HCC growth in vi-vo.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 negative-ly correlated with a poor prognosis of hepatocellular carcinoma patients.Compared with shNC group, cell prolif-eration, 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 transplan-tation, 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 prolif-eration, migration and invasion of HCC cells.It is promising to become a therapeutic target for HCC.

     

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