Chen Peng, Zhao Huasi, Huang Jingjing, Yan Xizhong, Zhang Yunfei, Gao Yongshun
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University Zhengzhou, China.
Department of Respiration, The First Affiliated Hospital of Zhengzhou University Zhengzhou, China.
Am J Cancer Res. 2016 Sep 1;6(9):2010-2020. eCollection 2016.
MicroRNA-17-5p (miR-17-5p) has previously been reported to play an important role in tumor development and progression. However, it functions differently regarding different kinds of malignant tumor, and its role and mechanism in gastric cancer (GC) still lacks investigation. In this study, we detected the relationship between miR-17-5p and the development of GC by qRT-PCR, and it turned out that the level of miR-17-5p was significantly higher in GC patients than that in normal controls, and the aberrant expression of miR-17-5p was correlated with lymph node metastasis. After that, we examined the effect of miR-17-5p taking on the proliferation, apoptosis, migration and invasion of GC cells and the underlying mechanism. Experiments indicated that knockdown of miR-17-5p inhibited the proliferation, invasion and migration, while promoting apoptosis of SGC7901 cells. Early Growth Response 2 (EGR2) protein or mRNA levels were downregulated or upregulated after overexpression or knockdown of miR-17-5p, respectively. By using dual luciferase assay and Western blot, we identified EGR2 as a functional target of miR-17-5p. As far as we know, this could be the first study to demonstrate that miR-17-5p is associated with tumor stage of GC and that it could possibly become a new therapeutic method for the treatment of GC.
此前有报道称,微小RNA-17-5p(miR-17-5p)在肿瘤发生和发展过程中发挥重要作用。然而,它在不同类型的恶性肿瘤中功能各异,其在胃癌(GC)中的作用及机制仍有待研究。在本研究中,我们通过定量逆转录聚合酶链反应(qRT-PCR)检测了miR-17-5p与胃癌发生发展之间的关系,结果显示,胃癌患者中miR-17-5p水平显著高于正常对照组,且miR-17-5p的异常表达与淋巴结转移相关。此后,我们研究了miR-17-5p对胃癌细胞增殖、凋亡、迁移和侵袭的影响及其潜在机制。实验表明,敲低miR-17-5p可抑制SGC7901细胞的增殖、侵袭和迁移,同时促进其凋亡。过表达或敲低miR-17-5p后,早期生长反应2(EGR2)蛋白或mRNA水平分别下调或上调。通过双荧光素酶报告基因检测和蛋白质印迹法,我们确定EGR2是miR-17-5p的功能靶点。据我们所知,这可能是第一项证明miR-17-5p与胃癌肿瘤分期相关且可能成为治疗胃癌新方法的研究。