In this study, we analyzed the role of circular RNAs in the growth and progression of bladder cancer. Direct Sanger sequencing and quantitative RT-PCR analysis showed that circ_0006332 was significantly upregulated in bladder cancer tissues. Sequencing analysis showed that circ_0006332 is generated from splicing of exons 8 and 9 of the MYBL2 transcript. Fluorescence in situ hybridization analysis showed that circ_0006332 was localized to the cytoplasm of bladder cancer cells. Dual luciferase reporter assays showed that miR-143 specifically bound to circ_0006332 and the 3'UTR of MYBL2. High expression of circ_006332 correlated with tumor-node-metastasis stages and muscular invasion in bladder cancer patients. Knockdown of circ_0006332 in bladder cancer cells decreased proliferation, colony formation and invasiveness. Circ_0006332 knockdown increased E-cadherin levels and decreased Vimentin, CCNB1 and P21 protein expression. This suggests that circ_0006332 promotes epithelial-mesenchymal transition and cell cycle progression. In vivo experiments in nude mice showed that circ_0006332 knockdown bladder cancer cells form significantly smaller tumors than the controls. Our study demonstrates that circ_0006332 promotes the growth and progression of bladder cancer by modulating MYBL2 expression by acting as a sponge for miR-143. Circ_0006332 is thus a potential early diagnostic marker of bladder cancer.
Keywords: MYBL2; bladder cancer; circ_0006332; invasion; proliferation.