circCD2AP promotes epithelial mesenchymal transition and stemness in bladder cancer by regulating FOXQ1/USP21 axis

Jinrong Wang; Jing Tan; Yichuan Zhang; Lei Zhou; Yuan Liu

doi:10.1016/j.isci.2023.108447

circCD2AP promotes epithelial mesenchymal transition and stemness in bladder cancer by regulating FOXQ1/USP21 axis

iScience. 2023 Nov 14;27(2):108447. doi: 10.1016/j.isci.2023.108447. eCollection 2024 Feb 16.

Authors

Jinrong Wang¹, Jing Tan¹, Yichuan Zhang¹, Lei Zhou¹, Yuan Liu¹

Affiliation

¹ Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China.

Abstract

Bladder cancer (BC) is a prevalent and deadly disease. circCD2AP was suggested to be highly expressed in BC. However, the exact mechanism needs further investigation. In this study, circCD2AP was observed to be upregulated in BC and linked to poor prognosis in individuals. Functionally, circCD2AP or USP21 knockdown inhibited BC cell EMT and stemness both in vitro and in vivo. Mechanistically, circCD2AP interacted with ELAVL1 to enhance the stability of USP21 mRNA, which, in turn, inhibited the ubiquitination degradation of FOXQ1. Through rescue assay, USP21 or FOXQ1 knockdown was found to abolish the promoting effects of circCD2AP or USP21 overexpression on BC cell EMT and stemness. Overall, this study has unveiled the role of circCD2AP/ELAVL1/USP21/FOXQ1 axis in BC EMT and stemness regulation, offering insights into the mechanisms underlying BC progression, with potential implications for therapeutic strategies.

Keywords: Cancer; Cell biology; Molecular biology.