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MicroRNA-598 通过直接靶向结肠癌转移相关基因 1(MACC1)抑制脑胶质瘤细胞的增殖和侵袭。

MicroRNA-598 Inhibits Cell Proliferation and Invasion of Glioblastoma by Directly Targeting Metastasis Associated in Colon Cancer-1 (MACC1).

机构信息

Department of Neurosurgery, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Hubei, P.R. China.

Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Hubei, P.R. China.

出版信息

Oncol Res. 2018 Sep 14;26(8):1275-1283. doi: 10.3727/096504018X15185735627746. Epub 2018 Feb 14.

Abstract

The dysregulation of microRNA (miRNA) expression is closely related with tumorigenesis and tumor development in glioblastoma (GBM). In this study, we found that miRNA-598 (miR-598) expression was significantly downregulated in GBM tissues and cell lines. Restoring miR-598 expression inhibited cell proliferation and invasion in GBM. Moreover, we validated that metastasis associated in colon cancer-1 (MACC1) is a novel target of miR-598 in GBM. Restoring MACC1 expression reversed the inhibitory effects of miR-598 overexpression on GBM cells. In addition, miR-598 overexpression suppressed Met/AKT pathway activation in GBM. Our results provided compelling evidence that miR-598 serves tumor-suppressive roles in GBM and that its antioncogenic effects are mediated chiefly through the direct suppression of MACC1 expression and regulation of the Met/AKT signaling pathway. Therefore, miR-598 is a potential target in the treatment of GBM.

摘要

miRNA(miRNA)表达失调与脑胶质瘤(GBM)的发生和发展密切相关。在本研究中,我们发现 miRNA-598(miR-598)在 GBM 组织和细胞系中的表达明显下调。恢复 miR-598 的表达可抑制 GBM 中的细胞增殖和侵袭。此外,我们验证了结肠癌转移相关基因 1(MACC1)是 miR-598 在 GBM 中的一个新靶基因。恢复 MACC1 的表达逆转了 miR-598 过表达对 GBM 细胞的抑制作用。此外,miR-598 过表达抑制了 GBM 中 Met/AKT 通路的激活。我们的研究结果为 miR-598 在 GBM 中发挥肿瘤抑制作用提供了有力的证据,其抗肿瘤作用主要是通过直接抑制 MACC1 的表达和调节 Met/AKT 信号通路来实现的。因此,miR-598 是治疗 GBM 的一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2c8/7844726/ad935f6e5a73/OR-26-1275-g001.jpg

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