Liu Yiwei, Chen Hairong, Li Xiangcheng, Zhang Feng, Kong Lianbao, Wang Xuehao, Bai Jin, Wu Xiaofeng
Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
Front Oncol. 2021 Feb 26;11:607021. doi: 10.3389/fonc.2021.607021. eCollection 2021.
Proteasome 26S subunit ATPase 2 (PSMC2) plays a pathogenic role in various cancers. However, its function and molecular mechanism in hepatocellular carcinoma (HCC) remain unknown. In this study, tissue microarray (TMA) analysis showed that PSMC2 is highly expressed in HCC tumors and correlates with poor overall and disease-free survival in HCC patients. Multivariate Cox regression analysis revealed that PSMC2 is an independent prognostic factor for HCC patients. Furthermore, our results showed that PSMC2 knockdown inhibited cell proliferation and suppressed tumorigenesis . Knockdown of PSMC2 increased the expression of p21 and therefore decreased the expression of cyclin D1. Dual-luciferase reporter assays indicated that depletion of PSMC2 significantly enhanced the promoter activity of p21. Importantly, PSMC2 knockdown-induced phenotypes were also rescued by downregulation of P21. Taken together, our data suggest that PSMC2 promotes HCC cell proliferation and cell cycle progression through the p21/cyclin D1 signaling pathway and could be a promising diagnostic and therapeutic target for HCC patients.
蛋白酶体26S亚基ATP酶2（PSMC2）在多种癌症中发挥致病作用。然而，其在肝细胞癌（HCC）中的功能和分子机制仍不清楚。在本研究中，组织芯片（TMA）分析显示PSMC2在HCC肿瘤中高表达，且与HCC患者较差的总生存期和无病生存期相关。多变量Cox回归分析显示PSMC2是HCC患者的独立预后因素。此外，我们的结果表明，敲低PSMC2可抑制细胞增殖并抑制肿瘤发生。敲低PSMC2可增加p21的表达，从而降低细胞周期蛋白D1的表达。双荧光素酶报告基因检测表明，PSMC2的缺失显著增强了p21的启动子活性。重要的是，下调P21也可挽救PSMC2敲低诱导的表型。综上所述，我们的数据表明，PSMC2通过p21/细胞周期蛋白D1信号通路促进HCC细胞增殖和细胞周期进程，可能是HCC患者有前景的诊断和治疗靶点。
