Journal
ONCOTARGET
Volume 7, Issue 19, Pages 27445-27457Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8479
Keywords
microRNA-31; integrin alpha 5; bladder cancer; chemotherapy; mitomycin-C
Categories
Funding
- National Natural Science Foundation of China [81472379]
- Leading Talent Project of Shanghai
Ask authors/readers for more resources
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 alpha 5 (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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available