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Research Paper|Volume 10, Issue 10|pp 2606—2623

Circular RNA circUBXN7 represses cell growth and invasion by sponging miR-1247-3p to enhance B4GALT3 expression in bladder cancer

Hongwei Liu1,2, Dongliang Chen3,4, Junming Bi1,2, Jinli Han1, Meihua Yang1,2, Wei Dong1,2, Tianxin Lin1,2, Jian Huang1
  • 1Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
  • 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
  • 3Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
  • 4State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China

* * Equal contribution

Received: July 12, 2018Accepted: September 24, 2018Published: October 12, 2018

Copyright: © 2018 Liu 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

Circular RNAs (circRNAs) have recently been confirmed to participate in different pathological processes, including cancer progression. However, the role and precise mechanism of action of the majority of circRNAs have not been elucidated in bladder cancer (BC). Here, we identified a novel circular RNA, termed circUBXN7, which was significantly downregulated in BC tissues compared with matched nontumor tissues. Importantly, we found that decreased circUBXN7 expression was associated with pathological stage, grade and poor prognosis of BC patients. Functional experiments showed that circUBXN7 overexpression dramatically inhibited proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Mechanistically, circUBXN7 could directly bind to miR-1247-3p and reverse the oncogenic effects induced by miR-1247-3p. Furthermore, B4GALT3 was predicted and confirmed to be a target of miR-1247-3p. Rescue experiments demonstrated that circUBXN7 abrogated miR-1247-3p-mediated inhibition of B4GALT3 expression. Finally, silencing of B4GALT3 promoted proliferation and invasion of BC cells; and partially abolished the tumor suppressive effects caused by circUBXN7. Taken together, our study revealed that circUBXN7 serves as a competitive endogenous RNA of miR-1247-3p to elevate B4GALT3 expression, consequently inhibiting cell viability and invasion in BC. The circUBXN7-miR-1247-3p-B4GALT3 regulatory network may provide a new perspective for gene-based treatment strategies for BC.