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微小RNA-187通过靶向胰岛素样生长因子-1受体抑制肝细胞癌的肿瘤生长和转移。

MicroRNA-187 inhibits tumor growth and metastasis via targeting of IGF-1R in hepatocellular carcinoma.

作者信息

Han Xinqiang, Wang Xuemin, Zhao Baolei, Chen Gang, Sheng Yuguo, Wang Wenming, Teng Mujian

机构信息

Department of Interventional Medicine and Vascular Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China.

Department of Gastroenterology, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):2241-2246. doi: 10.3892/mmr.2017.6788. Epub 2017 Jun 15.

DOI:10.3892/mmr.2017.6788
PMID:28627639
Abstract

Hepatocellular carcinoma (HCC) is the primary and most frequently occurring type of malignant liver cancer, accounting for 70-85% of total liver cancer cases worldwide. It has previously been demonstrated that the aberrant expression of microRNAs (miR) contributes to carcinogenesis and progression of various human malignancies, including HCC. However, mechanisms underlying the differential expression and specific roles of miR‑187 in HCC remain to be elucidated, particularly regarding how the modulation of malignant phenotypes in HCC cells occurs. The present study demonstrated that miR‑187 was significantly downregulated in HCC tissues and cell lines. Restoration of miR‑187 expression inhibited cell proliferation, migration and invasion in HCC. Furthermore, insulin‑like growth factor 1 receptor (IGF‑1R) was demonstrated to act as a direct target gene of miR‑187 in HCC. IGF‑1R knockdown mimicked the effects of miR‑187 overexpression in HCC, resulting in a significant inhibition of cell proliferation, migration and invasion. The results of the present study demonstrated that miR‑187 acted as a tumor suppressor in HCC progression via direct targeting of IGF‑1R. miR‑187 may therefore exhibit the potential to act as a novel and therapeutic target for HCC treatment in the future.

摘要

肝细胞癌(HCC)是原发性且最常见的恶性肝癌类型,占全球肝癌病例总数的70 - 85%。先前已有研究表明,微小RNA(miR)的异常表达会促进包括HCC在内的各种人类恶性肿瘤的发生和发展。然而,miR - 187在HCC中差异表达及特定作用的潜在机制仍有待阐明,尤其是HCC细胞中恶性表型是如何被调控的。本研究表明,miR - 187在HCC组织和细胞系中显著下调。恢复miR - 187的表达可抑制HCC细胞的增殖、迁移和侵袭。此外,胰岛素样生长因子1受体(IGF - 1R)被证明是HCC中miR - 187的直接靶基因。敲低IGF - 1R可模拟miR - 187过表达对HCC的影响,导致细胞增殖、迁移和侵袭受到显著抑制。本研究结果表明,miR - 187通过直接靶向IGF - 1R在HCC进展中发挥肿瘤抑制作用。因此,miR - 187未来可能具有作为HCC治疗新的治疗靶点的潜力。

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