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Research Paper|Volume 12, Issue 12|pp 11530—11549

Hsa_circ_0085576 promotes clear cell renal cell carcinoma tumorigenesis and metastasis through the miR-498/YAP1 axis

Guanghua Liu1, Jingmin Zhou1, Yuanlin Piao2, Xin Zhao1, Yuzhi Zuo1, Zhigang Ji1
  • 1Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, P.R. China
  • 2Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, P.R. China
Received: January 15, 2020Accepted: April 17, 2020Published: June 15, 2020

Copyright © 2020 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

There is emerging evidence that circular RNAs (circRNAs) act as important regulators in various cancers. It is less clear, however, what role circRNA plays in the tumorigenesis and metastasis of clear cell renal cell carcinoma (ccRCC). In this study, using bioinformatics analysis and a series of experimental analysis, we characterized a novel circRNA, hsa_circ_0085576 was up-regulated in ccRCC tissues and cell lines. High hsa_circ_0085576 expression was significantly correlated with tumor size, clinical stage, and metastasis status and poorer survival. Knockdown of hsa_circ_0085576 notably inhibited cell proliferation, migration, invasion, whereas enhanced cell apoptosis of ccRCC cells, in vitro. In contrast, overexpression of hsa_circ_0085576 had the opposite effects. Moreover, hsa_circ_0085576 silencing significantly suppressed tumor growth and metastasis, whereas overexpression of hsa_circ_0085576 had the opposite effects, in vivo, Our results further showed that hsa_circ_0085576 acted as a competitive endogenous RNAs to interact with microRNA-498, to attenuate its repressive effect on target gene Yes-associated protein 1 (YAP1). Finally, functional studies revealed that inhibition of hsa_circ_0085576 suppressed cell growth and metastasis by regulating miR-498/YAP1 signaling, in ccRCC cells. Based on these findings, hsa_circ_0085576 may represent a valuable prognostic biomarker and a potential therapeutic target to curb the tumorigenesis and metastasis of ccRCC.