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MicroRNA-561 inhibits gastric cancercell proliferation and invasion by downregulating c-Myc expression

机译:MicroRNA-561通过下调c-Myc表达抑制胃癌细胞的增殖和侵袭

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摘要

Gastric cancer (GC) causes nearly one million deaths worldwide each year. However, the molecular pathway of GC development remains unclear. Increasing evidences have shown that microRNAs (miRNAs) are highly associated with tumor development. However, relative little is known about the potential role of miRNAs in gastric cancer development. In the present study, we showed that miR-561 was down-regulated frequently in human GCs cell lines and tissues, and its expression was associated with tumor-node-metastasis (pTNM) stage. Enforced expression of miR-561 in GC cells inhibited cell proliferation and invasion in vitro. In contrast, knockdown of miR-561 had the opposite effect on cell proliferation and invasion. Moreover, c-Myc was identified as a potential miR-561 target. Further studies confirmed that miR-561 suppressed the expression of c-Myc by directly binding to its 3’-untranslated region. Restoration of c-Myc in miR-561-overexpressed GC cells reversed the suppressive effects of miR-561 and c-Myc was inversely correlated with miR-561 expression in GC tissues. These results demonstrate that miR-561 acts as a novel tumor suppressor in GC by targeting c-Myc gene and inhibiting GC cells proliferation and invasion. These findings contribute to current understanding of the functions of miR-561 in GC.
机译:全世界每年胃癌(GC)导致近一百万人死亡。然而,气相色谱发展的分子途径仍不清楚。越来越多的证据表明,microRNA(miRNA)与肿瘤的发展高度相关。但是,关于miRNA在胃癌发展中的潜在作用了解甚少。在本研究中,我们表明miR-561在人类GC细胞和组织中频繁下调,其表达与肿瘤淋巴结转移(pTNM)阶段有关。 miR-561在GC细胞中的强制表达在体外抑制细胞增殖和侵袭。相反,敲低miR-561对细胞增殖和侵袭具有相反的作用。此外,c-Myc被鉴定为潜在的miR-561靶标。进一步的研究证实,miR-561通过直接与其3'非翻译区结合而抑制c-Myc的表达。在miR-561过表达的GC细胞中恢复c-Myc可以逆转miR-561的抑制作用,而c-Myc与miR-561在GC组织中的表达呈负相关。这些结果表明,miR-561通过靶向c-Myc基因并抑制GC细胞的增殖和侵袭,在GC中充当新型的肿瘤抑制因子。这些发现有助于当前对GC中miR-561功能的了解。

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