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Research Paper|Volume 11, Issue 23|pp 11202—11223

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

Yinjie Su1, Weilian Feng2, Guanglei Zhong3, Yiyao Ya1,4, Zehu Du5, Juanyi Shi1, Luping Chen6, Wen Dong1, Tianxin Lin1
  • 1The Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
  • 2The Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
  • 3The Department of Gynecological oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
  • 4The Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
  • 5The Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
  • 6The Department of Pediatric Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
* Equal contribution
Received: September 1, 2019Accepted: November 18, 2019Published: December 10, 2019
https://doi.org/10.18632/aging.102525

Copyright © 2019 Su et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.