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MicroRNA-145-5p inhibits gastric cancer invasiveness through targeting N-cadherin and ZEB2 to suppress epithelial–mesenchymal transition

Authors Jiang S, He X, Xia Y, Hu W, Luo J, Zhang J, Tao H

Received 4 December 2015

Accepted for publication 8 March 2016

Published 18 April 2016 Volume 2016:9 Pages 2305—2315

DOI https://doi.org/10.2147/OTT.S101853

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 2

Editor who approved publication: Professor Min Li


Shi-Bin Jiang,1,2,* Xu-Jun He,1,3,* Ying-Jie Xia,1,3 Wei-Jian Hu,2 Jun-Gang Luo,1,2 Jun Zhang,2,3 Hou-Quan Tao1–3

1Department of Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, 2Wenzhou Medical University, Wenzhou, 3Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China

*These authors contributed equally to this work

Abstract: MicroRNA (miR)-145-5p has been reported to function as a suppressor of cancer and plays an important role in cancer invasiveness. Epithelial–mesenchymal transition (EMT) is an important process in cancer invasion and migration. However, the involvement of miR-145-5p in EMT in human gastric cancer (GC) remains unclear. In this study, we aimed to investigate the molecular mechanisms by which miR-145-5p regulates EMT in GC invasiveness. We used quantitative real-time polymerase chain reaction to investigate the miR-145-5p expression level in GC and matched normal tissues. The effects of miR-145-5p on GC cell invasion and migration abilities were evaluated using Transwell models. The relationships among miR-145-5p and zinc-finger E-box binding homeobox 2 (ZEB2), E-cadherin, and N-cadherin were analyzed by quantitative real-time polymerase chain reaction and Western blot analyses. miR-145-5p levels in primary GC tissues obtained from 60 patients were significantly downregulated, compared to those in paired normal tissues. Lauren classification, depth of tumor invasion, lymph node metastasis, lymphatic invasion, and tumor–node–metastasis stage were associated with miR-145-5p expression. miR-145-5p inhibits the expression of the candidate target gene ZEB2 to delay the invasion and migration of GC cells. ZEB2 acts as transcriptional repressor of E-cadherin, while miR-145-5p is known to suppress N-cadherin directly to regulate EMT. Therefore, we concluded that miR-145-5p may target N-cadherin and ZEB2 directly to influence EMT.

Keywords: miR-145-5p, zinc-finger E-box binding homeobox 2 (ZEB2), epithelial–mesenchymal transition (EMT), gastric cancer

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