Qian Kun, Mao Binglang, Zhang Wei, Chen Huanwen
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
The Medical Examination Center, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
Am J Transl Res. 2016 Sep 15;8(9):3802-3811. eCollection 2016.
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.
胃癌每年在全球导致近100万人死亡。然而,胃癌发生的分子途径仍不清楚。越来越多的证据表明,微小RNA(miRNA)与肿瘤发生高度相关。然而,关于miRNA在胃癌发生中的潜在作用相对知之甚少。在本研究中,我们发现miR-561在人胃癌细胞系和组织中经常下调,其表达与肿瘤-淋巴结-转移(pTNM)分期相关。在胃癌细胞中过表达miR-561可抑制体外细胞增殖和侵袭。相反,敲低miR-561对细胞增殖和侵袭有相反的作用。此外,c-Myc被确定为miR-561的潜在靶点。进一步研究证实,miR-561通过直接结合其3'-非翻译区抑制c-Myc的表达。在miR-561过表达的胃癌细胞中恢复c-Myc可逆转miR-561的抑制作用,且c-Myc与胃癌组织中miR-561的表达呈负相关。这些结果表明,miR-561通过靶向c-Myc基因并抑制胃癌细胞增殖和侵袭,在胃癌中发挥新型肿瘤抑制因子的作用。这些发现有助于当前对miR-561在胃癌中功能的理解。