ciRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653

Background: Circular RNAs have been widely explored as potential biomarkers and therapeutic targets in bladder cancer; however, few have been functionally characterized. Results: ciRs-6 is expressed at low levels in cancer tissues and advanced tumor grades and stages, and its expression correlates with better outcomes for bladder cancer patients. In vitro and in vivo, ciRs-6 was shown to suppress bladder cancer growth by sponging miR-653 to elevate March1 levels. March1 is an E3 ubiquitin ligase that has been proven to suppress bladder cancer growth; knocking down March1 in ciRs-6 overexpressed bladder cancer cells reversed the tumor suppressive effect of ciRs-6. Conclusions: Our study identifies an oncogenic role of ciRs-6 and suggests its usefulness as a novel biomarker for bladder cancer diagnosis and prognosis and as a therapeutic target for bladder cancer. Methods: ciRs-6 was identified by RNA-seq and qPCR; CCK8 assays, clone forming assays and cell cycle analyses were performed to evaluate the in vitro effect of ciRs-6 in bladder cancer; further, a mouse subcutaneous tumor model was designed for in vivo analysis. RNA pulldown assays, miRNA capture experiments and dual luciferase assessments were applied for mechanistic studies.