Open AccessMicroRNA-31 functions as a tumor suppressor and increases sensitivity to mitomycin-C in urothelial bladder cancer by targeting integrin α5
Author(s) -
Tingting Xu,
Liang Qin,
Zhaowei Zhu,
Xianjin Wang,
Yue Liu,
Yong Fan,
Shan Zhong,
Xiaojing Wang,
Xiaohua Zhang,
Leilei Xia,
Xiang Zhang,
Chen Xu,
Shen Zhang
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.8479
Subject(s) - bladder cancer , mitomycin c , suppressor , integrin , microrna , cancer research , medicine , urothelial cancer , cancer , oncology , biology , gene , receptor , biochemistry , surgery
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.