MicroRNA-216a inhibits the metastasis of gastric cancer cells by targeting JAK2/STAT3-mediated EMT process
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Youmao Tao1, Songbai Yang2, Yuanyu Wu1, Xuedong Fang1, Yannan Wang1, Yan Song1 and Tao Han2
1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China
2Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China
Tao Han, email: email@example.com
Keywords: miR-216a, tumor metastasis, gastric cancer, JAK2/STAT3, epithelial-mesenchymal transition
Received: July 27, 2017 Accepted: August 28, 2017 Published: October 04, 2017
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.
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