Journal Article

Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p

Liu, Xuefeng, Zhang, Bin, Sun, Ming, Zhao, Wenyan, Deng, Peng

2022

Overview

Bladder cancer (BC) is one of the most common malignant tumors of the urinary system, and cisplatin (CDDP) is a critical chemical drug for the treatment of BC. However, CDDP-resistance seriously limits the therapeutic efficacy of this drug for clinical utilization. Thus, identification of pivotal molecule targets that regulate CDDP-resistance in BC become urgent and necessary. In this study, we firstly identified a novel BC-associated circular RNA circ_0058063 that participates in the regulation of CDDP-resistance in BC. Specifically, circ_0058063 was significantly overexpressed in CDDP-resistant tissue and cells, in contrast with the corresponding CDDP-sensitive counterparts. Further loss-of-function experiments validated that downregulation of circ_0058063 suppressed cell proliferation and tumor growth, whereas induced cell apoptosis in the CDDP-resistant BC cells in vitro and in vivo . In addition, we disclosed that circ_0058063 acts as a sponge for miR-335-5p to positively regulate B2M expression, and further rescuing experiments verified that the enhancing effects of sh-circ_0058063 on CDDP-sensitivity in the CDDP-resistant BC cells were abrogated by silencing miR-335-5p. Taken together, our results demonstrated that circ_0058063 contributed to CDDP resistance of bladder cancer cells via sponging miR-335-5p, and B2M might be the downstream effector gene. This study firstly evidenced that targeting circ_0058063 might be an effective strategy to improve CDDP-sensitivity in BC.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Analysis / Antibodies / Apoptosis / Beta globulins / Binding sites / Biomedical and Life Sciences / Biomedicine / Bladder cancer / Cancer / Cancer cells / Cancer Research / Cancer therapies / Care and treatment / Cell growth / Cell Proliferation / Chemotherapy / Circular RNA / Cisplatin / Cisplatin - pharmacology / Colorectal cancer / Diagnosis / Disease / Drug Resistance, Neoplasm / Gastric cancer / Health Promotion and Disease Prevention / Hospitals / Humans / Hybridization / Immunotherapy / Medicine/Public Health / MicroRNA / MicroRNAs / MicroRNAs - genetics / Oncology / Ovarian cancer / Radiation therapy / Risk factors / RNA, Circular - genetics / Surgical Oncology / Tumors / Urinary Bladder Neoplasms - drug therapy / Urinary Bladder Neoplasms - genetics / Urinary Bladder Neoplasms - pathology