Han Shuangxi, Ding Xuemei, Wang Shaohong, Xu Li, Li Wenxiao, Sun Wenbing
Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100043, People's Republic of China.
Department of Hepatobiliary Surgery, Binzhou Central Hospital, Binzhou 251700, People's Republic of China.
Cancer Manag Res. 2020 Sep 21;12:8685-8693. doi: 10.2147/CMAR.S254617. eCollection 2020.
MicroRNAs (miRNAs) are key modulators for gene expression via inducing translational repression or target gene degradation. miR-133a-3p was reported to stimulate or inhibit cancer progression but its role in hepatocellular carcinoma (HCC) remains to be explored.
Quantitative real-time PCR (RT-qPCR) was utilized to explore miR-133a-3p expression level in HCC cells. Dual-luciferase activity reporter assay was used to validate the direct interaction between miR-133a-3p and coronin-like actin-binding protein 1C (CORO1C). In addition, we analyzed the expression levels of miR-133a-3p and CORO1C in HCC tissues and normal tissues on the UCALAN website. Functional assays including cell counting kit-8 assay, colony formation assay, flow cytometry analysis and transwell invasion assay were conducted to explore the biological functions of miR-133a-3p in HCC.
miR-133a-3p was found to have downregulated expression in HCC tissues and cells. Meanwhile, we showed that low miR-133a-3p levels were correlated with poorer overall survival of HCC patients. Overexpression of miR-133a-3p suppressed HCC cell growth and invasion but promoted cell apoptosis via targeting CORO1C.
Our results revealed a novel mechanism of miR-133a-3p in regulating HCC progression and provided evidence that miR-133a-3p functions as a tumor suppressor in HCC.
微小RNA(miRNA)是通过诱导翻译抑制或靶基因降解来调控基因表达的关键因子。据报道,miR-133a-3p可促进或抑制癌症进展,但其在肝细胞癌(HCC)中的作用仍有待探索。
采用定量实时聚合酶链反应(RT-qPCR)检测HCC细胞中miR-133a-3p的表达水平。利用双荧光素酶活性报告基因检测法验证miR-133a-3p与冠蛋白样肌动蛋白结合蛋白1C(CORO1C)之间的直接相互作用。此外,我们在UCALAN网站上分析了HCC组织和正常组织中miR-133a-3p和CORO1C的表达水平。通过细胞计数试剂盒-8检测、集落形成检测、流式细胞术分析和Transwell侵袭检测等功能实验,探索miR-133a-3p在HCC中的生物学功能。
发现miR-133a-3p在HCC组织和细胞中的表达下调。同时,我们发现低水平的miR-133a-3p与HCC患者较差的总生存率相关。miR-133a-3p的过表达通过靶向CORO1C抑制HCC细胞的生长和侵袭,但促进细胞凋亡。
我们的研究结果揭示了miR-133a-3p调控HCC进展的新机制,并提供了证据表明miR-133a-3p在HCC中发挥肿瘤抑制作用。