Growing evidence suggests that circular RNAs (circRNAs) play pivotal roles in cancer progression. In this study, bioinformatic analysis identified a dysregulated circRNA termed circPTPRA in bladder cancer (BC). By using qRT-PCR analysis, we verified that circPTPRA is down-regulated in clinical BC specimens compared with the matched non-tumor samples, while correlation analyses showed that low circPTPRA expression is associated with poor prognosis, advanced tumor stage and larger tumor size. Based on these findings, we conducted functional assays and revealed that circPTPRA inhibits BC cell proliferation in vitro and tumor growth in vivo. In addition, RNA pull-down, miRNA capture, FISH, and luciferase reporter assays demonstrated that circPTPRA can directly sponge miR-636. Cell transfection experiments showed that miR-636 promotes the proliferation of BC cells by decreasing the expression of Krüppel Like Factor 9 (KLF9) upon binding to the 3'UTR of its mRNA.Further analysis confirmed that circPTPRA competitively sponges miR-636 to upregulate the KLF9 expression, leading to decreased proliferation of BC cells. Our investigation indicates that circPTPRA acts as a tumor suppressor in BC, and suggests that this circRNA may be a novel prognostic biomarker and therapeutic target in BC.
Keywords: KLF9; bladder cancer; circPTPRA; miR-636; proliferation.