Research Paper|Volume 13, Issue 15|pp 19908—19919

A circular RNA, circSMARCA5, inhibits prostate cancer proliferative, migrative, and invasive capabilities via the miR-181b-5p/miR-17-3p-TIMP3 axis

Xin Xie¹, Fu-Kang Sun¹, Xin Huang¹, Cheng-He Wang¹, Jun Dai¹, Ju-Ping Zhao¹, Chen Fang¹, Wei He¹

¹Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China

* Co-first author

Received: March 31, 2021Accepted: July 30, 2021Published: August 13, 2021

https://doi.org/10.18632/aging.203408

Copyright: © 2021 Xie 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

SMARCA5 (circSMARCA5) is involved in the occurrence of different cancers, but its role in prostate cancer carcinogenesis and metastatic transformation remains elusive. Thus, we evaluated the circSMARCA5 functional relevance in prostate cancer and its associated molecular mechanism. First, circSMARCA5 expression and function in this cancer were evaluated. To determine the miR-181b-5p/miR-17-3p target and clarify how circSMARCA5 regulates the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis, RNA immunoprecipitation, biotin-coupled microRNA capture, luciferase reporter, Western blot, and quantitative real-time PCR assays were employed. In primary and metastatic prostate cancer tissues, circSMARCA5 was significantly downregulated compared with normal controls. Functionally, circSMARCA5 exhibited a suppressive effect on prostate cancer cells' metastasis and growth. At the molecular level, circSMARCA5 could affect the tissue inhibitor of metalloproteinases 3 (TIMP3) expression through miR-181b-5p or miR-17-3p interactions. Moreover, lysine acetyltransferase 5 (KAT5) induced circSMARCA5 biogenesis and regulated the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis. These results suggested that targeting circSMARCA5-miR-181b-5p-TIMP3 and circSMARCA5-miR-17-3p-TIMP3 axis might be a novel therapeutic strategy for prostate cancer.