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微小RNA-642通过调节SEMA4C和p38丝裂原活化蛋白激酶信号通路在肝细胞癌中发挥肿瘤抑制作用。

miR-642 serves as a tumor suppressor in hepatocellular carcinoma by regulating SEMA4C and p38 MAPK signaling pathway.

作者信息

Yu Zaijun, Du Yuehe, Li Hongying, Huang Jichao, Jiang Deqing, Fan Jilong, Shen Yuelan, Zhang Lingling, Yu Xiujuan, Xu Na, Ke Qungang

机构信息

Department of Hepatobiliary Surgery, The Second People's Hospital of Lianyungang, Lianyungang, Jiangsu 222006, P.R. China.

Department of Emergency Office, Center for Disease Control and Prevention of Lianyungang, Lianyungang, Jiangsu 222003, P.R. China.

出版信息

Oncol Lett. 2020 Oct;20(4):74. doi: 10.3892/ol.2020.11935. Epub 2020 Jul 30.

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and high risk. Study of the role and mechanism of miRNAs are a hot spot of research providing new treatment ideas in malignant tumors. The effect of miR-642a on HCC progression and the underlying molecular mechanism were investigated. Expression of miR-642a and SEMA4C was measured by western blot analysis and RT-PCR. miR-642a expression was elevated while SEMA4C expression was attenuated in HCC tissues and cells. Results of luciferase reporter and western blot analyses show that miR-642a modulated SEMA4C expression by binding to its 3'UTR. Moreover, miR-642a negatively regulated SEMA4C expression. HCC cell migration and invasion was tested by Transwell assays. The findings revealed that the number of migrated and invaded cells were reduced by miR-642a mimic and raised by miR-642a inhibitor, indicating that miR-642a showed a suppression effect on HCC cell migration and invasion. Additionally, the migration and invasion of HCC cells were inhibited by SEMA4C siRNA, and SEMA4C reversed miR-642a effect on HCC migration and invasion. Furthermore, p38 MAPK signaling pathway was proven to be inhibited by miR-642a mimic, whereas facilitated by miR-642a inhibitor and SEMA4C siRNA could overturn the promotion effect of miR-642a inhibitor. Briefly, miR-642a targeted SEMA4C to repress HCC cell migration and invasion through p38 MAPK signaling pathway providing a new strategy for treatment of HCC patients.

摘要

肝细胞癌(HCC)是一种发病率高且风险高的恶性肿瘤。对微小RNA(miRNA)的作用和机制的研究是一个研究热点,为恶性肿瘤提供了新的治疗思路。本研究探讨了miR-642a对HCC进展的影响及其潜在分子机制。通过蛋白质印迹分析和逆转录-聚合酶链反应(RT-PCR)检测miR-642a和SEMA4C的表达。在HCC组织和细胞中,miR-642a表达升高,而SEMA4C表达减弱。荧光素酶报告基因和蛋白质印迹分析结果表明,miR-642a通过与SEMA4C的3'非翻译区(3'UTR)结合来调节其表达。此外,miR-642a负向调节SEMA4C的表达。通过Transwell实验检测HCC细胞的迁移和侵袭能力。研究结果显示,miR-642a模拟物可减少迁移和侵袭细胞的数量,而miR-642a抑制剂则增加了迁移和侵袭细胞的数量,这表明miR-642a对HCC细胞的迁移和侵袭具有抑制作用。此外,SEMA4C小干扰RNA(siRNA)可抑制HCC细胞的迁移和侵袭,且SEMA4C可逆转miR-642a对HCC迁移和侵袭的影响。此外,miR-642a模拟物可抑制p38丝裂原活化蛋白激酶(MAPK)信号通路,而miR-642a抑制剂则促进该信号通路,且SEMA4C siRNA可逆转miR-642a抑制剂的促进作用。简而言之,miR-642a靶向SEMA4C,通过p38 MAPK信号通路抑制HCC细胞的迁移和侵袭,为HCC患者的治疗提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f151/7436928/28cfa4c66736/ol-20-04-11935-g00.jpg

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