1. Academic Validation
  2. MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting MAML3 and WHSC1 in gastric cancer

MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting MAML3 and WHSC1 in gastric cancer

  • FASEB J. 2017 Sep;31(9):3774-3786. doi: 10.1096/fj.201601140RR.
Jinjing Li 1 Tingyu Li 1 Yuanyuan Lu 1 Gaofei Shen 1 Hao Guo 1 Jian Wu 1 Chao Lei 1 Feng Du 1 Fenli Zhou 1 Xiaodi Zhao 2 Yongzhan Nie 3 Daiming Fan 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
  • 2 State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China leedyzhao@fmmu.edu.cn.
  • 3 State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China yongznie@fmmu.edu.cn.
Abstract

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.-Li, J., Li, T., Lu, Y., Shen, G., Guo, H., Wu, J., Lei, C., Du, F., Zhou, F., Zhao, X., Nie, Y., Fan, D. MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting MAML3 and WHSC1 in gastric Cancer.

Keywords

EMT; invasion; microRNA; migration.

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