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微小RNA-154通过直接靶向MTDH抑制胃癌细胞的生长和转移。

MicroRNA-154 inhibits the growth and metastasis of gastric cancer cells by directly targeting MTDH.

作者信息

Qiao Wenhui, Cao Nong, Yang Lei

机构信息

Department of General Surgery, The First Hospital of Lanzhou University, Chengguan, Lanzhou, Gansu 730000, P.R. China.

出版信息

Oncol Lett. 2017 Sep;14(3):3268-3274. doi: 10.3892/ol.2017.6558. Epub 2017 Jul 8.

Abstract

MicroRNAs (miRNAs) are a group of non-protein-coding, highly conserved single-stranded RNA molecules. The abnormal expression of miRNAs has been demonstrated to have an important function in the carcinogenesis and progression of gastric cancer. microRNA-154 (miR-154) has been reported to be downregulated in non-small cell lung, colorectal and prostate cancer. However, the expression and roles of miR-154 in gastric cancer remain to be established. The present study measured the expression levels of miR-154 in gastric cancer tissues and cell lines. miR-154 was found to be significantly downregulated in gastric cancer tissues and cell lines. In addition, functional studies indicated that the overexpression of miR-154 inhibited the proliferation, migration and invasion of gastric cancer cells. Using TargetScan, a dual luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis, metadherin (MTDH) was revealed as a novel miR-154 target. In addition, knocking down MTDH lead to a similar effect as overexpressing-154 in gastric cells. The present findings indicate that miR-154 was downregulated in gastric cancer, and inhibited tumor behaviors of gastric cancer cells partially through the downregulation of MTDH. Therefore, the miR-154/MTDH axis may be a novel therapeutic to treat patients with gastric cancer.

摘要

微小RNA(miRNA)是一组非蛋白质编码的、高度保守的单链RNA分子。已证明miRNA的异常表达在胃癌的发生和发展中具有重要作用。据报道,微小RNA-154(miR-154)在非小细胞肺癌、结直肠癌和前列腺癌中表达下调。然而,miR-154在胃癌中的表达及作用仍有待确定。本研究检测了miR-154在胃癌组织和细胞系中的表达水平。发现miR-154在胃癌组织和细胞系中显著下调。此外,功能研究表明,miR-154的过表达抑制了胃癌细胞的增殖、迁移和侵袭。通过TargetScan、双荧光素酶报告基因检测、逆转录-定量聚合酶链反应和蛋白质印迹分析,发现黏附素(MTDH)是miR-154的一个新靶点。此外,敲低MTDH在胃癌细胞中产生的效果与过表达miR-154相似。本研究结果表明,miR-154在胃癌中表达下调,并通过下调MTDH部分抑制胃癌细胞的肿瘤行为。因此,miR-154/MTDH轴可能是治疗胃癌患者的一种新的治疗方法。

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