title: MicroRNA-31 functions as a tumor suppressor and increases sensitivity to mitomycin-C in urothelial bladder cancer by targeting integrin α5.
abstract: 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.
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xianjin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhoujun
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D016685:Mitomycin / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D011379:Prognosis; D011897:Random Allocation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D039482:Integrin alpha5; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D016685:Mitomycin
keywords: bladder cancer; chemotherapy; integrin α5; microRNA-31; mitomycin-C