Chen Ping, Liu Yayue, Ma Xiaochen, Li Qingli, Zhang Yangfan, Xiong Qingqing, Song Tianqiang
Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Biosci Trends. 2021 Sep 22;15(4):249-256. doi: 10.5582/bst.2021.01139. Epub 2021 May 30.
Replication Factor c4 (RFC4) has been found to play important roles in many carcinomas and is correlated with poor prognosis. The present study was performed to investigate the specific role of RFC4 in hepatocellular carcinoma (HCC) and the underlying molecular mechanism. Public datasets including TCGA and GTEx were applied to explore the expression of RFC4 in HCC and its association with HCC prognosis. The results of bioinformatics analysis showed that RFC4 was overexpressed in HCC tissues compared with noncancerous tissues and significantly correlated with poor prognosis for HCC. Through immunohistochemistry, the association between RFC4 expression and clinical-pathological features of HCC patients was evaluated. Western blots were applied to investigate relative protein expression. Then in vivo and in vitro experiments were performed to explore the function of RFC4 in HCC tumor cells. The present results suggest that high level expression of RFC4 is associated with tumor size. In addition, RFC4 knockdown suppressed the cell proliferation and sphere formation of hepatoma cells in vitro. Moreover, silencing of RFC4 significantly decreased the growth of tumors in a xenograft tumor model. In conclusion, our study indicates that RFC4 is a potential prognostic predictor associated with poor outcomes for HCC patients. Furthermore, knocking down RFC4 could significantly inhibit tumor progression both in vitro and in vivo. Therefore, the present study can shed new light on the understanding of molecular mechanisms of HCC and may provide molecular targets and diagnostic biomarkers for the treatment of HCC.
复制因子c4（RFC4）已被发现在许多癌症中发挥重要作用，且与预后不良相关。本研究旨在探讨RFC4在肝细胞癌（HCC）中的具体作用及其潜在的分子机制。应用包括TCGA和GTEx在内的公共数据集来探究RFC4在HCC中的表达及其与HCC预后的关联。生物信息学分析结果显示，与癌旁组织相比，RFC4在HCC组织中高表达，且与HCC的不良预后显著相关。通过免疫组织化学评估RFC4表达与HCC患者临床病理特征之间的关联。应用蛋白质免疫印迹法研究相关蛋白表达。然后进行体内和体外实验以探究RFC4在HCC肿瘤细胞中的功能。目前的结果表明，RFC4的高水平表达与肿瘤大小相关。此外，RFC4基因敲低抑制了体外肝癌细胞的增殖和球状体形成。而且，在异种移植肿瘤模型中，RFC4沉默显著降低了肿瘤生长。总之，我们的研究表明，RFC4是与HCC患者不良预后相关的潜在预后预测指标。此外，敲低RFC4可在体外和体内显著抑制肿瘤进展。因此，本研究可为理解HCC的分子机制提供新的线索，并可能为HCC治疗提供分子靶点和诊断生物标志物。
