Yuan Bo, Bo Wentao, Feng Xielin, Hu Yong, Zeng Jiawei
Department of General Practice, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Department of Hepatopancreatobiliary Surgery, Sichuan Provincial Cancer Hospital, Chengdu, Sichuan 610041, P.R. China.
Oncol Lett. 2020 Dec;20(6):382. doi: 10.3892/ol.2020.12245. Epub 2020 Oct 23.
Hepatocellular carcinoma is a serious public health problem in China. The mortality rate associated with the majority of cancer types has decreased as a result of targeted therapy. However, the mortality rates associated with hepatocellular carcinoma have not improved; therefore, the identification of new molecular targets is required for the development of novel targeted therapies. In the present study, a new molecular target, Rhophilin Rho GTPase-binding protein 2 (RHPN2), was identified. The levels of RHPN2 protein in tumor tissues were assessed via immunohistochemistry, while the mRNA levels were analyzed via reverse transcription-quantitative PCR. Additionally, cell viability was tested via MTT analysis. RHPN2 expression was upregulated in hepatocellular carcinoma tissues compared with that of matched adjacent normal tissues. More importantly, low expression of RHPN2 in patients with hepatocellular carcinoma was associated with an improved prognosis rate compared with patients with high expression. Downregulation of RHPN2 reduced the proliferation of hepatocellular carcinoma cells and increased the rate of apoptosis, whereas overexpression of RHPN2 demonstrated the opposite effects. Hepatocyte nuclear factor 1α was implicated in the mechanism of RHPN2. Overall, these data indicated that overexpression of RHPN2 may promote hepatocellular carcinoma.
肝细胞癌在中国是一个严重的公共卫生问题。由于靶向治疗,大多数癌症类型的死亡率有所下降。然而,肝细胞癌相关的死亡率并未改善;因此,开发新型靶向治疗需要鉴定新的分子靶点。在本研究中,鉴定出了一个新的分子靶点,即Rho鸟嘌呤核苷酸交换因子2(RHPN2)。通过免疫组织化学评估肿瘤组织中RHPN2蛋白的水平,同时通过逆转录定量PCR分析mRNA水平。此外,通过MTT分析检测细胞活力。与配对的相邻正常组织相比,肝细胞癌组织中RHPN2表达上调。更重要的是,与高表达患者相比,肝细胞癌患者中RHPN2低表达与改善的预后率相关。RHPN2的下调降低了肝癌细胞的增殖并增加了凋亡率,而RHPN2的过表达则表现出相反的效果。肝细胞核因子1α参与了RHPN2的机制。总体而言,这些数据表明RHPN2的过表达可能促进肝细胞癌。