J Cancer 2016; 7(12):1740-1746. doi:10.7150/jca.15620
MiR-193a-5p Targets the Coding Region of AP-2α mRNA and Induces Cisplatin Resistance in Bladder Cancers
1. College of Life Science, Hunan Normal University, Changsha 410081, Hunan, China;
2. Hunan Provincial People's Hospital, Changsha 410005, Hunan, China
3. Hunan Cancer Hospital, Changsha 410013, Hunan, China.
Zhou J, Duan H, Xie Y, Ning Y, Zhang X, Hui N, Wang C, Zhang J, Zhou J. MiR-193a-5p Targets the Coding Region of AP-2α mRNA and Induces Cisplatin Resistance in Bladder Cancers. J Cancer 2016; 7(12):1740-1746. doi:10.7150/jca.15620. Available from http://www.jcancer.org/v07p1740.htm
Transcription factor AP-2 alpha (AP-2α or TFAP2A) is a newly identified prognostic marker of chemotherapy; its expression is positively correlated with chemosensitivity and survival of cancer patients. Using computational programs, we predicted that the coding region of AP-2α gene contains a potential miRNA response element (MRE) of miR-193a-5p, and the single nucleotide polymorphism (SNP) site (c.497A>G, rs111681798) resides within the predicted MRE. The results of luciferase assays and Western blot analysis demonstrated that miR-193a-5p negatively regulated the expression of AP-2α proteins, but have no influence on the mutant AP-2α (c.497A>G). Infection with lentiviral AP-2α gene or miR-193a-5p inhibitor in the bladder cancer cells decreased migration and cisplatin resistance, while knockdown of AP-2α gene or overexpression of miR-193a-5p in the urothelial cell line SV-HUC-1 increased migration and cisplatin resistances. We concluded that miR-193a-5p induced cisplatin resistance by repressing AP-2α expression in bladder cancer cells.
Keywords: miR-193a-5p, AP-2α, cisplatin resistance, bladder cancer, single nucleotide polymorphism.