MicroRNA-21 promotes TGF-β1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression.
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.
Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China.
Chang
C
Li
Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China.
Lei
L
Song
Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China.
Zhuo
Z
Zhang
Department of Cadre Ward, The First Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China.
Xiao-Xue
XX
Bai
Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China.
Ming-Fu
MF
Cui
Department of Endoscopics, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China.
Lian-Jun
LJ
Ma
D000328:Adult; D000368:Aged; D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
MicroRNA-21; PTEN; TGF-β1; epithelial-mesenchymal transition; gastric cancer