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miR-186 通过直接靶向 CDK6 抑制肝癌细胞的增殖、迁移、侵袭和 EMT。

miR-186 Represses Proliferation, Migration, Invasion, and EMT of Hepatocellular Carcinoma via Directly Targeting CDK6.

机构信息

Department of Vascular Surgery, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong UniversityJinanP.R. China.

Department of Gastroenterology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong UniversityJinanP.R. China.

出版信息

Oncol Res. 2020 Dec 10;28(5):509-518. doi: 10.3727/096504020X15954139263808. Epub 2020 Jul 22.

Abstract

The present study aimed to investigate the effect of miR-186 on proliferation, migration, invasion, and epithelialmesenchymal transition (EMT) of hepatocellular carcinoma (HCC). In this work, miR-186 was downregulated in HCC tissues and cells, and low miR-186 level helped predict the occurrence of vascular invasion and poor prognosis in patients with HCC. miR-186 overexpression inhibited cell proliferation and tumor growth in nude mice, repressed migration and invasion abilities, and enhanced apoptosis in HCC cells. miR-186 also retarded progression of EMT. miR-186 directly bound to the 3-untranslated regions of cyclin-dependent kinase 6 (CDK6) to inhibit its expression. Overexpression of CDK6 markedly reversed inhibitory effects of miR-186 on proliferation, apoptosis, migration, and invasion of HCC cells. Conversely, inhibition of CDK6 exerted synergic effect on the biological functions of miR-186. In conclusion, miR-186 represses proliferation, migration, invasion, and EMT, and induces apoptosis through targeting CDK6 in HCC, which may provide a new therapeutic target for HCC.

摘要

本研究旨在探讨 miR-186 对肝细胞癌 (HCC) 增殖、迁移、侵袭和上皮间质转化 (EMT) 的影响。在这项工作中,miR-186 在 HCC 组织和细胞中下调,低 miR-186 水平有助于预测 HCC 患者发生血管侵犯和预后不良。miR-186 过表达抑制裸鼠中的细胞增殖和肿瘤生长,抑制迁移和侵袭能力,并增强 HCC 细胞的凋亡。miR-186 还延缓 EMT 的进展。miR-186 直接与细胞周期蛋白依赖性激酶 6 (CDK6) 的 3'-非翻译区结合,抑制其表达。CDK6 的过表达显著逆转了 miR-186 对 HCC 细胞增殖、凋亡、迁移和侵袭的抑制作用。相反,抑制 CDK6 对 miR-186 的生物学功能具有协同作用。总之,miR-186 通过靶向 CDK6 抑制 HCC 中的增殖、迁移、侵袭和 EMT,并诱导细胞凋亡,这可能为 HCC 提供新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7559/7751224/9aa5ae757656/OR-28-509-g001.jpg

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