MiR-23a regulates TGF-β-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells

Cao,Mengru; Seike,Masahiro; Soeno,Chie; Mizutani,Hideaki; Kitamura,Kazuhiro; Minegishi,Yuji; Noro,Rintaro; Yoshimura,Akinobu; Cai,Li; Gemma,Akihiko

doi:10.3892/ijo.2012.1535

MiR-23a regulates TGF-β-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells

Authors:
- Mengru Cao
- Masahiro Seike
- Chie Soeno
- Hideaki Mizutani
- Kazuhiro Kitamura
- Yuji Minegishi
- Rintaro Noro
- Akinobu Yoshimura
- Li Cai
- Akihiko Gemma
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Affiliations: Department of Internal Medicine, Division of Pulmonary Medicine/Infection and Oncology, Nippon Medical School, Tokyo 113-8603, Japan, Department of Medical Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin, P.R. China
Published online on: June 28, 2012 https://doi.org/10.3892/ijo.2012.1535
Pages: 869-875
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) has been shown to be related to the pathogenesis of various diseases including lung cancer. Recently, microRNAs (miRNA) have been recognized as a new class of genes involved in human tumorigenesis. MiR-23a/24/27a is a miRNA cluster located in chromosome 19p13.12, which can function as an oncogene in several human cancers. In this study, we analyzed miR-23a/24/27a expression in 10 non-small cell cancer (NSCLC) cell lines by real-time PCR analysis. Correlation between expression of these miRNAs and TGF-β/Smad signaling was evaluated. We found that miR-23a could be regulated by TGF-β1 in a Smad-dependent manner in A549 lung adenocarcinoma cells showing the EMT phenomenon. Knockdown of miR-23a partially restored E-cadherin expression under conditions of TGF-β1 stimulation. In contrast, overexpression of miR-23a could suppress E-cadherin expression and stimulate EMT. Furthermore, A549 cells with overexpressed miR-23a were more resistant to gefitinib compared to the parental cells. These findings suggest that miR-23a regulates TGF-β-induced EMT by targeting E-cadherin in lung cancer cells and may be useful as a new therapeutic target in NSCLC.

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