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microRNA-802 通过靶向 RUNX3 促进肝癌生长。

microRNA-802 accelerates hepatocellular carcinoma growth by targeting RUNX3.

机构信息

Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.

出版信息

J Cell Physiol. 2020 Oct;235(10):7128-7135. doi: 10.1002/jcp.29611. Epub 2020 Jan 31.

DOI:10.1002/jcp.29611
PMID:32003017
Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Prognosis is often unfavorable. In this study, the effects of microRNA-802 (miR-802) on HCC progression were assessed in vivo and in vitro. miR-802 was found to be significantly upregulated in HCC tumor tissue compared to paired adjacent nontumor tissue. In vitro, transfection with a miR-802 mimic accelerated SMMC-7721 cellular proliferation, increased accumulation of the cell-cycle S-phase cell populations, as well as cell migration. In vivo injection of a miR-802 agomir promoted HCC proliferation in nude mice. Targets of miR-802 were predicted by miRWalk, miRanda, RNA22, and Targetscan. By luciferase reporter assay RUNX3 was identified as a direct target of miR-802. As judged by western blot analysis, RUNX3 was upregulated when miR-802 was inhibited. These data demonstrate increased miR-802 expression in patients with HCC and that miR-802 overexpression promotes tumor cell growth, in a RUNX3-dependent manner.

摘要

肝细胞癌(HCC)是全球最常见的恶性肿瘤之一。预后通常不佳。在这项研究中,评估了 microRNA-802(miR-802)在体内和体外对 HCC 进展的影响。与配对的相邻非肿瘤组织相比,HCC 肿瘤组织中 miR-802 的表达明显上调。在体外,用 miR-802 模拟物转染可加速 SMMC-7721 细胞增殖,增加细胞周期 S 期细胞群体的积累以及细胞迁移。体内注射 miR-802 激动剂可促进裸鼠 HCC 的增殖。通过 miRWalk、miRanda、RNA22 和 Targetscan 预测 miR-802 的靶标。通过荧光素酶报告基因测定,RUNX3 被鉴定为 miR-802 的直接靶标。通过 Western blot 分析判断,当 miR-802 被抑制时,RUNX3 上调。这些数据表明 HCC 患者中 miR-802 的表达增加,并且 miR-802 过表达以 RUNX3 依赖的方式促进肿瘤细胞生长。

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