Qiao Wenhui, Cao Nong, Yang Lei
Department of General Surgery, The First Hospital of Lanzhou University, Chengguan, Lanzhou, Gansu 730000, P.R. China.
Oncol Lett. 2017 Sep;14(3):3268-3274. doi: 10.3892/ol.2017.6558. Epub 2017 Jul 8.
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.
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。