miR-142-5p通过DNA甲基转移酶1抑制胃癌细胞增殖迁移的机制研究

miR-142-5p inhibits proliferation and migration of gastric cancer cells through DNMT1

目的:探究miR-142-5p在胃癌(GC)细胞中的作用并研究其机制。方法:qRT-PCR检测miR-142-5p表达;CCK-8和Transwell实验研究miR-142-5p对细胞增殖及迁移的影响;双荧光素酶报告基因和Western blot验证miR-142-5p的作用靶点。结果:miR-142-5p在GC组织及细胞系中的表达分别低于人正常胃组织及胃正常上皮黏膜细胞系GES-1,且其表达水平与胃癌肿瘤大小及淋巴结转移密切相关。在MKN28细胞中过表达miR-142-5p及在BGC-823细胞中沉默miR-142-5p能够分别抑制及促进胃癌细胞的增殖和迁移。DNA甲基转移酶1(DNMT1)是miR-142-5p直接作用靶点,miR-142-5p能够直接调节DNMT1的表达,并通过DNMT1调控胃癌细胞增殖及迁移。结论:miR-142-5p在GC中的表达降低,并在胃癌细胞中发挥抑癌基因的作用,能够通过抑制DNMT1来抑制胃癌细胞的增殖和迁移。

AIM:To investigate the role of miR-142-5p in gastric cancer(GC)cells and its mechanism.METHODS:The expression of miR-142-5p was detected by qRT-PCR;the effects of microRNA-142-5p on cell proliferation and migration were studied by CCK8 and Transwell assays;and the target of miR-142-5p was confirmed by dual luciferase reporter assay gene and Western blot assays.RESULTS:The expression of miR-142-5p in GC tissue and cell line was lower than that in normal gastric tissues and GES-1 cells,and the expression level of miR-142-5p was closely related to tumor size and lymph node metastasis.Overexpression of miR-142-5p in MKN28 cells and silencing miR-142-5p in BGC-823 cells inhibited and promoted the proliferation and migration of gastric cancer cells,respectively.DNA methyltransferase 1(DNMT1)was the direct target of miR-142-5p,which could directly be regulated by miR-142-5p,and miR-142-5p regulated the proliferation and migration of gastric cancer cells through DNMT1.CONCLUSION:miR-142-5p is decreased in GC,implying an anti-oncogenetic effect to inhibit the proliferation and migration of gastric cancer cells by inhibiting DNMT1.