Fang Jian-Feng, Zhao Hai-Ping, Wang Zheng-Fei, Zheng Shu-Sen
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Mol Med Rep. 2017 May;15(5):2720-2726. doi: 10.3892/mmr.2017.6320. Epub 2017 Mar 14.
RAS protein activator like 2 (RASAL2) has been reported to be dysregulated in various types of cancer. It has previously been demonstrated that RASAL2 is hypomethylated in hepatocellular carcinoma (HCC). However, the expression pattern of RASAL2 and its potential role in HCC remain to be elucidated. The present study demonstrated that the expression of RASAL2 was upregulated in HCC tissues, compared with in normal liver tissues, by using immunohistochemistry. In addition, Cell Counting Kit-8 assay and invasion assay revealed that knockdown of RASAL2 inhibited the growth and invasion of HCC cells. Western blotting results indicated that the inhibition of RASAL2 reduced the levels of phosphorylated-AKT. Notably, RASAL2 was observed to be a direct target of miR-203 in HCC in luciferase activity assays. Furthermore, overexpression of miR-203 exhibited a similar effect to RASAL2 knockdown in HCC cells. These results indicated that RASAL2 serves a tumor oncogenic role in HCC and may be considered a potential target in HCC.
据报道,RAS蛋白激活剂样2(RASAL2)在多种类型的癌症中表达失调。先前已证明,RASAL2在肝细胞癌(HCC)中存在低甲基化现象。然而,RASAL2的表达模式及其在HCC中的潜在作用仍有待阐明。本研究通过免疫组织化学表明,与正常肝组织相比,RASAL2在HCC组织中的表达上调。此外,细胞计数试剂盒-8检测和侵袭实验表明,敲低RASAL2可抑制HCC细胞的生长和侵袭。蛋白质印迹结果表明,抑制RASAL2可降低磷酸化AKT的水平。值得注意的是,荧光素酶活性检测显示,RASAL2是HCC中miR-203的直接靶点。此外,miR-203的过表达在HCC细胞中表现出与敲低RASAL2类似的效果。这些结果表明,RASAL2在HCC中发挥肿瘤致癌作用,可能被视为HCC的潜在治疗靶点。