MicroRNA-31 functions as a tumor suppressor and increases sensitivity to mitomycin-C in urothelial bladder cancer by targeting integrin α5.

Urothelial bladder cancer (UBC) is a common genitourinary malignancy. MiR-31, a well-identified miRNA, exhibits diverse properties in different cancers. However, the specific functions and mechanisms of miR-31 in UBC have not been investigated.

In this study, tumor samples, especially invasive UBC, showed significantly reduced level of miR-31, as compared with normal urothelium. Prognostic analysis using the EORTC model showed that down-regulation of miR-31 correlated with higher risks of recurrence and progression in noninvasive UBC cases. Remarkably, overexpression of miR-31 mimics in UBC cell lines inhibited cell proliferation, migration and invasion. Integrin α5 (ITGA5), an integrin family member, was subsequently identified as a direct target of miR-31 in UBC cells. When treated with mitomycin-C (MMC), miR-31-expressing UBC cells displayed lower survival and higher apoptotic rates, and deactivated Akt and ERK. These effects arising from miR-31 overexpression were abrogated by ITGA5 restoration. Furthermore, miR-31 markedly inhibited tumor growth and increased the effectiveness of MMC in UBC xenografts. In summary, our data suggest that miR-31 is a prognostic predictor and can serve as a potential therapeutic target of UBC.

Oncotarget. 2016 Mar 30 [Epub ahead of print]

Tianyuan Xu, Liang Qin, Zhaowei Zhu, Xianjin Wang, Yue Liu, Yong Fan, Shan Zhong, Xiaojing Wang, Xiaohua Zhang, Leilei Xia, Xiang Zhang, Chen Xu, Zhoujun Shen

Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Shanghai Key Laboratory of Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Shanghai Key Laboratory of Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Shanghai Key Laboratory of Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, China., Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.