MicroRNA-216a inhibits the metastasis of gastric cancer cells by targeting JAK2/STAT3-mediated EMT process

被引:49
作者
Tao, Youmao [1 ]
Yang, Songbai [2 ]
Wu, Yuanyu [1 ]
Fang, Xuedong [1 ]
Wang, Yannan [1 ]
Song, Yan [1 ]
Han, Tao [2 ]
机构
[1] Jilin Univ, China Japan Union Hosp, Dept Gastrointestinal Colorectal & Anal Surg, Changchun 130033, Jilin, Peoples R China
[2] Jilin Univ, China Japan Union Hosp, Dept Vasc Surg, Changchun 130033, Jilin, Peoples R China
关键词
miR-216a; tumor metastasis; gastric cancer; JAK2/STAT3; epithelial-mesenchymal transition; EPITHELIAL-MESENCHYMAL TRANSITION; PANCREATIC TUMOR-GROWTH; HEPATOCELLULAR-CARCINOMA; SIGNALING PATHWAY; INVASION; APOPTOSIS; MIR-216A; EXPRESSION; RESISTANCE; MIGRATION;
D O I
10.18632/oncotarget.21488
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs (miRNAs), a group of small, non-protein coding, endogenous RNAs, play critical roles in the tumorigenesis and progression of human cancer. miR-216a has recently been reported to play an oncogenic role in human cancer. While, the expression of miR-216a, its biological function and underlying molecular mechanisms in gastric cancer (GC) are largely unknown. In this study, we revealed that miR-216a was underexpressed in GC tissues compared to matched noncancerous tissues. Decreased levels of miR-216a were confirmed in GC cell lines compared with a normal gastric epithelium cell line. miR-216a underexpression was associated with malignant prognostic features including lymph node metastasis, venous infiltration, invasive depth and advanced TNM stage. GC patients with low miR-216a level showed an obvious shorter overall survival. miR-216a overexpression restrained migration and invasion of MGC-803 cells, while its knockdown exerted opposite effects on metastatic behaviors of SGC-7901 cells. In vivo experiments found that miR-216a restoration reduced metastatic nodes of GC cells in nude mice liver. miR-216a notably suppressed epithelial-mesenchymal transition (EMT) of GC cells. Janus kinase 2 (JAK2) was recognized as a direct target and downstream mediator of miR-216a in GC cells. Interestingly, JAK2/signal transducer and activator of transcription 3 (STAT3) pathway was prominently inactivated by miR-216a and probably mediated the role of miR-216a in the regulation of migration, invasion and EMT process of GC cells. In conclusion, these data suggest that miR-216a functions as a tumor suppressive miRNA in the development of GC possibly by targeting JAK2/STAT3-mediated EMT.
引用
收藏
页码:88870 / 88881
页数:12
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