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

• Published in: The FASEB journal 2017-09, Vol.31 (9), p.3774-3786
• Main Authors: Li, Jinjing, Li, Tingyu, Lu, Yuanyuan, Shen, Gaofei, Guo, Hao, Wu, Jian, Lei, Chao, Du, Feng, Zhou, Fenli, Zhao, Xiaodi, Nie, Yongzhan, Fan, Daiming
• Format: Article
• Language: English
• Subjects: Cancer; Cell Line, Tumor; Cell Movement; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; E-cadherin; EMT; Epithelial-Mesenchymal Transition - physiology; Gastric cancer; Gene Expression Regulation, Neoplastic; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Humans; invasion; Mesenchyme; Metastases; Metastasis; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; migration; miRNA; Neoplasm Invasiveness; Neoplasm Metastasis - physiopathology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Regulators; Repressor Proteins - genetics; Repressor Proteins - metabolism; Repressors; Restoration; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Stomach Neoplasms - metabolism; Tissues; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201601140RR

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. FASEB J. 31, 3774–3786 (2017). www.fasebj.org—Branco, Renato Chaves Souto, Camargo, Rafael Ludemann, Batista, Thiago Martins, Vettorazzi, Jean Franciesco, Borck, Patricia Cristine, dos Santos‐Silva, Junia Carolina Rebelo, Boschero, Antonio Carlos, Zoppi, Claudio Cesar, Carneiro, Everardo Magalhäes MiR‐2392 suppresses metastasis and epithelial–mesenchymal transition by targeting MAML3 and WHSC1 in gastric cancer. FASEB J. 31, 3774–3786 (2017)