Novel circRNA_0071196/miRNA-19b-3p/CIT axis is associated with proliferation and migration of bladder cancer

Circular RNAs (circRNAs) are non-coding RNAs that are connected at the 3′ and 5′ ends by an exon or intron. Studies increasingly show that circRNAs play an important role in tumorigenesis by acting as a 'sponge' for microRNAs (miRNAs), which abrogates the latter's effect on their target mRNAs. To identify a possible circRNA/miRNA/mRNA network in bladder cancer (BCa), we analyzed the circRNA and mRNA expression profiles of BCa and adjacent normal bladder tissues. A total of 127 circRNAs and 1,612 mRNAs were differentially expressed in the tumor tissues, and were primarily associated with cancer-related pathways. A competing endogenous RNAs (ceRNA) network was then constructed which predicted a regulatory axis of circRNA_0071196, miRNA-19b-3p and its target gene citron Rho-interacting serine/threonine kinase (CIT). Luciferase reporter assay validated the relationship between circRNA_0071196 and miRNA-19b-3p and of the latter with CIT. Furthermore, CIT was overexpressed in the BCa tissues, and was found to be correlated with metastasis and tumor histological grade. Knockdown of CIT in the human bladder cancer cell line 5367 significantly inhibited the proliferation, migration and colony formation capacity of the cells, and also upregulated the mediators of the p53 and RhoA-ROCK signaling cascades that regulate cell cycle and migration. Taken together, our findings indicate that circRNA-0071196 upregulates CIT levels in BCa by sponging off miRNA-19b-3p, and the circRNA_0071196/miRNA-19b-3p/CIT axis is a potential therapeutic target in BCa.