期刊
FASEB JOURNAL
卷 31, 期 9, 页码 3774-3786出版社
WILEY
DOI: 10.1096/fj.201601140RR
关键词
microRNA; migration; invasion; EMT
资金
- National Natural Science Foundation of China [81430072, 81120108005, 81602641, 81572929]
- National Key Basic Research Program of China [2014CBA02002]
MicroRNAs have emerged as essential regulators of various cellular processes. We identified the role and underlying mechanisms of miR-2392 in gastric cancer (GC) metastasis. MiR-2392 was down-regulated in GC cell lines and tissues, and overexpression of miR-2392 significantly inhibited GC invasion and metastasis in vitro and in vivo. We identified MAML3 and WHSC1 as novel targets of miR-2392, and knockdown of MAML3 and WHSC1 had the same antimetastatic effect as that of miR-2392 in GC cells. These effects were clinically relevant, as low miR-2392 expression was correlated with high MAML3 and WHSC1 expression and poor survival in patients with GC. Furthermore, forced expression of miR-2392 substantially suppressed Slug and Twist1, transcriptional repressors of E-cadherin, by targeting MAML3 and WHSC1, respectively, resulting in inhibition of the epithelial-mesenchymal transition. These findings indicate that the miR-2392-MAML3/WHSC1-Slug/Twist1 regulatory axis plays a critical role in GC metastasis. Restoration of miR-2392 may be a therapeutic approach for blocking GC metastasis.
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