MicroRNA-21 promotes TGF-β1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression
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Chang Li1, Lei Song2, Zhuo Zhang 3, Xiao-Xue Bai4, Ming-Fu Cui1, Lian-Jun Ma5
1Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China
2Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China
3Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China
4Department of Cadre Ward, The First Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China
5Department of Endoscopics, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China
Lian-Jun Ma, email: [email protected]
Keywords: gastric cancer, epithelial-mesenchymal transition, MicroRNA-21, PTEN, TGF-β1
Received: March 10, 2016 Accepted: August 09, 2016 Published: September 07, 2016
This study aimed to explore the effects of miR-21 and PTEN/Akt signaling pathway on TGF-β1-induced epithelial-mesenchymal transition (EMT) in gastric cancer (GC). GC tissues and adjacent tissues were collected from 83 patients. The qRT-PCR assay was performed to detect miR-21 expression. The expressions of PTEN, Akt and p-Akt were detected by immunohistochemistry. After 48 h of treatment with TGF-β1 (10 ng/mL), the SGC-7901 and KATO-III cells were divided into the blank, negative control (NC), miR-21 inhibitors, PTEN-siRNA and miR-21 inhibitors + PTEN-siRNA groups. EMT related factors and PTEN expressions were detected by qRT-PCR assay and Western blotting. The scratch test was conducted to observe cell migration. Xenograft tumor model in nude mice was used to evaluate the effects of miR-21 on EMT of GC cells in vivo. In GC tissues, the expressions of miR-21, Akt and p-Akt were up-regulated, while PTEN expression was down-regulated. Gene and protein expressions of E-cadherin and PTEN in the miR-21 inhibitors group were higher than the blank, NC, PTEN-siRNA and miR-21 inhibitors + PTEN-siRNA groups, while the expressions of N-cadherin, β-catenin, Vimentin and Slug in the miR-21 inhibitors group were lower than other groups. MiR-21 inhibitors significantly inhibit cell migration and invasion in GC cell lines. In vivo xenograft experiment revealed that miR-21 inhibitor inhibits the growth of transplanted tumor through up-regulating E-cadherin and PTEN expressions and down-regulating the expressions of N-cadherin, β-catenin, Vimentin and Slug. These results suggest that miR-21 could promote TGF-β1-induced EMT in GC cells through up-regulating PTEN expression.
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