The miR-203/SNAI2 axis regulates prostate tumor growth, migration, angiogenesis and stemness potentially by modulating GSK-3β/β-CATENIN signal pathway

• Published in: IUBMB life Vol. 70; no. 3; p. 224
• Main Authors: Tian, Xinxin, Tao, Fangfang, Zhang, Baotong, Dong, Jin-Tang, Zhang, Zhiqian
• Format: Journal Article
• Language: English
• Published: England 01.03.2018
• Subjects: Aged; Animals; Apoptosis - genetics; beta Catenin - genetics; Carcinogenesis - genetics; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3 beta - genetics; Humans; Male; Mice; MicroRNAs - genetics; Middle Aged; Neoplastic Stem Cells - pathology; Neovascularization, Pathologic - genetics; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Signal Transduction - genetics; Snail Family Transcription Factors - genetics; Xenograft Model Antitumor Assays; MiR-203/SNAI2 axis; prostate cancer; GSK-3β/β-CATENIN signal pathway; angiogenesis; cancer stemness
• ISSN: 1521-6551
• DOI: 10.1002/iub.1720

Dysregulation of microRNA expression plays a pivotal role in the initiation and progression of a variety of human carcinomas including prostate cancer. Our previous studies have demonstrated that the silence of miR-203 contributes to the invasiveness of malignant breast cancer cells by targeting SNAI2. However, the effects and underlying mechanisms of miR-203/SNAI2 axis in prostate cancer have not been elucidated. The aim of this study is to explore the effects of miR-203/SNAI2 axis on the biological characteristics of prostate carcinomas both in vitro and in vivo. We found that miR-203 was significantly downregulated in prostate cancer cell lines compared with immortalized prostate epithelial cells using semi-quantitative PCR and real-time PCR, as well as in clinical prostate cancer tissues compared to normal tissues using TCGA analysis. Functionally, miR-203 inhibited prostate cancer cell proliferation, migration, endothelial cell tube formation and cancer stemness in vitro. Meanwhile, overexpression of miR-203 suppressed SNAI2 expression both in DU145 and PC3 cells. In addition, the in vivo study showed that miR-203 suppressed tumorigenicity, metastasis and angiogenesis of DU145 cells. Ectopic expression of SNAI2 rescued the inhibitory effects of miR-203 both in vitro and in vivo. Importantly, the EMT markers CDH1 and VIMENTIN were modulated by the miR-203/SNAI2 axis. Furthermore, the GSK-3β/β-CATENIN signal pathway was suppressed by miR-203 and could be reactivated by SNAI2. Taken together, this research unveiled the function of miR-203/SNAI2 axis in tumorigenesis, angiogenesis, stemness, metastasis and GSK-3β/β-CATENIN signal pathway in prostate cancer and gave insights into miR-203/SNAI2-targeting therapy for prostate cancer patients. © 2018 IUBMB Life, 70(3):224-236, 2018.