OncoTargets and Therapy (Oct 2019)
Circular RNA circ-Foxo3 induced cell apoptosis in urothelial carcinoma via interaction with miR-191-5p
Abstract
Chunyang Wang,1 Weiyang Tao,2 Shaobin Ni,1 Qiyin Chen1 1Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province 150001, People’s Republic of China; 2Department of Breast Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150001, People’s Republic of ChinaCorrespondence: Chunyang WangDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, No.23 Youzheng Street, Harbin, Heilongjiang Province 150001, People’s Republic of ChinaTel +86 1 524 511 0305Email [email protected]: Circular RNAs (circRNAs) play a critical role in cancer. Emerging evidence has shown circ-Foxo3, a circRNA, was dysregulated in a variety of tumor types. However, the exact role of circ-Foxo3 in bladder cancer has never been studied.Methods: We measured the expression level of circ-Foxo3 in human and murine bladder cancer tissues and in various human bladder cancer cell lines. We induced bladder cancer in mice by a carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). circ-Foxo3 was overexpressed in mice by lentiviral gene transfer and in cultured cells via overexpression plasmid. The effect of circ-Foxo3 on apoptosis was examined via apoptotic marker staining, Western blot, and flow cytometry. We further characterized the interaction between circ-Foxo3 and miR-191 and its functional impact on bladder cancer cells.Results: circ-Foxo3 was downregulated in bladder cancer in vivo and in vitro, and was upregulated in response to apoptotic stress. Overexpression of circ-Foxo3 promoted bladder cancer cell apoptosis in BBN mice and in human bladder cancer cell lines. miR-191-5p suppressed circ-Foxo3 expression and the pro-apoptotic effect of circ-Foxo3 in bladder cancer cells via directly targeting the 3ʹ-untranslated region (3ʹ-UTR) of circ-Foxo3.Conclusion: circ-Foxo3 was downregulated in bladder cancer in vivo and in vitro, and promoted bladder cancer apoptosis via direct interaction with miR-191. circ-Foxo3 could be a potential therapeutic target for bladder cancer.Keywords: bladder cancer, circular RNA, apoptosis, circ-Foxo3, miR-191
