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
复制标题
MiR-2392 通过靶向 MAML3 和 WHSC1 抑制胃癌的转移和上皮间质转化
DOI：
10.1096/fj.201601140rr
复制
发表时间：
2017-09-01
期刊：
影响因子：
4.8
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Li, Jinjing;Li, Tingyu;Fan, Daiming
microRNA已经成为各种细胞过程的重要调节因子。我们确定了miR-2392在胃癌（GC）转移中的作用和潜在机制。miR-2392在胃癌细胞系和组织中表达下调，miR-2392过表达可显著抑制胃癌的侵袭和转移。我们发现MAML 3和WHSC 1是miR-2392的新靶点，并且在GC细胞中敲低MAML 3和WHSC 1具有与miR-2392相同的抗转移作用。这些效应具有临床相关性，因为低miR-2392表达与GC患者中的高MAML 3和WHSC 1表达和低生存率相关。此外，miR-2392的强制表达通过分别靶向MAML 3和WHSC 1而显著抑制了E-钙粘蛋白的转录抑制因子Slug和Twist 1，从而抑制了上皮-间充质转化。这些发现表明miR-2392-MAML 3/WHSC 1-Slug/Twist 1调节轴在GC转移中起关键作用。miR-2392的恢复可能是阻断GC转移的治疗方法。
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.