Li Shuang, Zhang Haiyang, Ning Tao, Wang Xinyi, Liu Rui, Yang Haiou, Han Yueting, Deng Ting, Zhou Likun, Zhang Le, Bai Ming, Wang Xia, Ge Shaohua, Ying Guoguang, Ba Yi
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Cell Physiol Biochem. 2016;40(6):1303-1315. doi: 10.1159/000453183. Epub 2016 Dec 19.
MicroRNAs (miRNAs) have been demonstrated to play a crucial role in tumorigenesis. Previous studies have shown that miR-520b/e acts as a tumor suppressor in several tumors. Other studies indicated that epidermal growth factor receptor (EGFR) is highly expressed in many tumors, and involved in the development of tumors, such as cell proliferation, migration, angiogenesis and apoptosis. However, the correlation of miRNAs and EGFR in gastric cancer (GC) has not been adequately investigated. Our aim was to explore the relationship.
The expression levels of EGFR and miR-520b/e were examined by RT-PCR and Western blot. We also investigated the relationship between EGFR and miR-520b/e in GC cell lines by relevant experiments.
In this study, we found that miR-520b/e inhibits the protein expression of EGFR by directly binding with the 3'-untranslated region (3'-UTR). And it was shown that the down-regulation of miR-520b/e promotes cell proliferation and migration by negative regulation of the EGFR pathway, while over-expression of miR-520b/e inhibits these properties. In addition, the biological function of EGFR in GC cell lines was validated by silencing and over-expression assays respectively.
Taken together, our results demonstrate that miR-520b/e acts as a tumor suppressor by regulating EGFR in GC, and provide a novel marker and insight for the potential therapeutic target of GC.
微小RNA(miRNA)已被证明在肿瘤发生过程中起关键作用。先前的研究表明,miR-520b/e在多种肿瘤中作为肿瘤抑制因子发挥作用。其他研究表明,表皮生长因子受体(EGFR)在许多肿瘤中高表达,并参与肿瘤的发展,如细胞增殖、迁移、血管生成和凋亡。然而,miRNA与胃癌(GC)中EGFR的相关性尚未得到充分研究。我们的目的是探讨它们之间的关系。
通过逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法检测EGFR和miR-520b/e的表达水平。我们还通过相关实验研究了GC细胞系中EGFR与miR-520b/e之间的关系。
在本研究中,我们发现miR-520b/e通过直接与3'-非翻译区(3'-UTR)结合来抑制EGFR的蛋白表达。结果表明,miR-520b/e的下调通过对EGFR途径的负调节促进细胞增殖和迁移,而miR-520b/e的过表达则抑制这些特性。此外,分别通过沉默和过表达实验验证了EGFR在GC细胞系中的生物学功能。
综上所述,我们的结果表明miR-520b/e在GC中通过调节EGFR发挥肿瘤抑制作用,并为GC潜在的治疗靶点提供了一种新的标志物和见解。