miR186 suppresses prostate cancer progression by targeting Twist1

// Xian Zhao 1, * , Yanli Wang 1, * , Rong Deng 1 , Hailong Zhang 1 , Jinzhuo Dou 1 , Haihua Yuan 1 , Guofang Hou 1 , Yuzhang Du 1 , Qin Chen 1 , Jianxiu Yu 1, 2, 3, 4 1 Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 2 State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 3 Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China 4 Institute of Oncology & Department of Oncology, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China * These authors have contributed equally to this work Correspondence to: Jianxiu Yu, e-mail: Jianxiu.Yu@gmail.com Keywords: prostate cancer (PCa), microRNA (miRNA), metastasis, miR186, Twist1 Received: November 22, 2015     Accepted: April 04, 2016     Published: April 21, 2016 ABSTRACT Prostate cancer (PCa) is the second leading cause of cancer-related deaths in north American men, and most its related deaths are due to advanced and metastatic PCa. However, the molecular mechanisms underlying PCa progression are still unclear. Here we use a pair of prostate cell lines P69/M12, which have the same genetic background and the highly metastatic cell line M12 is a subline derived from P69, to identify the pathogenesis of PCa. We find that a key miRNA--miR186 is significantly reduced in M12 compared to that in P69. Further, we validate that miR186 is also downregulated in human PCa specimens, most significantly in the metastatic patient specimens. The low miR186 expression is correlated with poor patient survival. Through knockdown or overexpression of miR186 in PCa cell lines, we discover that miR186 strongly inhibits cell motility, invasive, soft-agar colony formation, 3D culture growth and vasculogenic mimicry (VM) formation capacity, as well as the epithelial-to-mesenchymal transition (EMT) process by downregulation of its target Twist1. Moreover, the inverse relationship between the expression levels of miR186 and Twist1 is confirmed in vivo tumor metastasis experiment and clinical specimens. Taken together, our findings demonstrate an important role of miR186/Twist1 axis in the regulation of PCa progression, suggesting a potential application of miR186/Twist1 in PCa treatment.