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微小RNA-204通过靶向食管癌中的叉头框蛋白M1抑制侵袭和上皮-间质转化。

miR-204 inhibits invasion and epithelial-mesenchymal transition by targeting FOXM1 in esophageal cancer.

作者信息

Sun Yurong, Yu Xiuwen, Bai Qingyang

机构信息

Department of Pathology, Qiqihar Medical University Qiqihar 161006, Heilongjiang, China.

出版信息

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12775-83. eCollection 2015.

Abstract

MicroRNAs (miRNAs), endogenous noncoding small RNAs, have been reported to play crucial roles in epithelial-mesenchymal transition (EMT) in cancers. Deregulation of microRNA-204 (miR-204) has been documented in many cancers, but its role in the development of esophageal cancer (EC) has not been studied. Here, we reported the role of miR-204 in invasion and EMT in EC. We identified an inverse correlation between miR-204 expression level and the invasion and EMT phenotype of EC cells, and up-regulation of miR-204 inhibited invasion and EMT phenotype of EC cells. Furthermore, we showed that forkhead box protein M1 (FOXM1) was a direct target gene of miR-204, and miR-204 regulated invasion and EMT in EC by acting directly on the 3'UTR of FOXM1 mRNA and suppressing its protein expression. We also explored the anti-tumor effect of miR-204, and found that overexpression of miR-204 suppressed the growth of esophageal tumors in vivo. These findings suggest that miR-204 might be a suppressor of invasion and EMT in EC, which offers a novel potential therapeutic target for EC.

摘要

微小RNA(miRNA)是内源性非编码小RNA,据报道在癌症的上皮-间质转化(EMT)中发挥关键作用。在许多癌症中都有微小RNA-204(miR-204)失调的记录,但它在食管癌(EC)发生发展中的作用尚未得到研究。在此,我们报道了miR-204在EC侵袭和EMT中的作用。我们发现miR-204表达水平与EC细胞的侵袭和EMT表型呈负相关,miR-204的上调抑制了EC细胞的侵袭和EMT表型。此外,我们表明叉头框蛋白M1(FOXM1)是miR-204的直接靶基因,miR-204通过直接作用于FOXM1 mRNA的3'非翻译区(3'UTR)并抑制其蛋白表达来调节EC的侵袭和EMT。我们还探究了miR-204的抗肿瘤作用,发现miR-204的过表达在体内抑制了食管肿瘤的生长。这些发现表明miR-204可能是EC侵袭和EMT的抑制因子,这为EC提供了一个新的潜在治疗靶点。

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