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微小RNA-367通过/PI3K/AKT信号通路促进肝细胞癌进展。

MicroRNA-367 promotes progression of hepatocellular carcinoma through /PI3K/AKT signaling pathway.

作者信息

Wang Zhihua, Luo Yu

机构信息

Hunan Provincial Tumor Hospital, Changsha, China.

Hunan Provincial Tumor Hospital, Changsha, China

出版信息

Biosci Rep. 2019 Sep 20. doi: 10.1042/BSR20182466.

Abstract

The study aimed to investigate the functional roles of micorRNA (miR)-367 in progression of hepatocellular carcinoma (HCC), as well as its regulation on PI3K/AKT pathway. The relative expression of  in HCC tissues and cell line was detected using quantitative real-time polymerase chain reaction (qRT-PCR) method. Chi-square test was applied to analyze the relationship between expression and clinical characterizes of HCC patients. The influences of  expression on cell proliferation, migration and invasion were analyzed using MTT and transwell assays respectively. Western blot assay was performed to for protein analysis. HCC tissues and cell lines exhibited significant up-regulation of Moreover, the elevated expression of  was positively correlated with tumor size ( =0.005), metastasis ( =0.004) and TNM stage ( 0.001). Knockdown of  expression could inhibit cell proliferation, migration and invasion in vitro. While, enhanced  expression exhibited opposite effects. Besides, inhibition of  might enhance  expression, reduce the levels of p-GSK3β and p-AKT.  might be a target of  in HCC. The inhibition of  could reverse the anti-tumor action caused by the knockdown of    serves as an oncogene in HCC through activating the PI3K/AKT pathway by targeting .

摘要

本研究旨在探讨微小RNA(miR)-367在肝细胞癌(HCC)进展中的功能作用及其对PI3K/AKT信号通路的调控。采用定量实时聚合酶链反应(qRT-PCR)法检测HCC组织和细胞系中miR-367的相对表达。应用卡方检验分析miR-367表达与HCC患者临床特征之间的关系。分别采用MTT法和Transwell法分析miR-367表达对细胞增殖、迁移和侵袭的影响。采用蛋白质免疫印迹法进行蛋白质分析。HCC组织和细胞系中miR-367均显著上调。此外,miR-367表达升高与肿瘤大小(P = 0.005)、转移(P = 0.004)和TNM分期(P 0.001)呈正相关。敲低miR-367表达可抑制体外细胞增殖、迁移和侵袭。而增强miR-367表达则表现出相反的作用。此外,抑制miR-367可能会增强GSK3β和AKT的表达,降低p-GSK3β和p-AKT的水平。GSK3β可能是HCC中miR-367的一个靶点。抑制GSK3β可逆转miR-367敲低所引起的抗肿瘤作用。miR-367通过靶向GSK3β激活PI3K/AKT信号通路,在HCC中作为癌基因发挥作用。

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