Abstract C088: circWSB1 promotes tumor progression in ccRCC via circWSB1/miR-182-5p/WSB1 axis

Abstract

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent urological carcinomas with a low overall 5-year survival rate, and its prognosis remains dismal. circular RNA (circRNA) has been discovered to be important regulators in ccRCC. However, the specific regulatory mechanisms of circRNA and its impact on phenotypes require further in-depth research. Methods: circRNA microarray sequencing analysis was used in this study to explore the expression pattern of circRNA in ccRCC. circWSB1 was discovered, and we evaluated its derivation, potential diagnostic efficacy, and prognostic significance in ccRCC tissues using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and sanger sequencing. Fluorescence in situ hybridization analysis (FISH), RNA immunoprecipitation, and dual-luciferase reporter gene assays were used to investigate the subcellular localization and regulation mechanism of circWSB1. In vivo and in vitro loss-of-function and gain-of-function experiments were used to determine the biological functions of circWSB1. Results: Through RNA sequencing of five pairs of tumor and adjacent tissues, we discovered that circWSB1 is highly expressed in ccRCC. We identified that circWSB1 interacts with miR-182-5p and upregulates the expression of its host gene, WSB1. Through models in vivo and in vitro, we found circWSB1 increases WSB1 expression via the circWSB1/miR-182-5p/WSB1 axis, which promotes ccRCC cell proliferation and migration. The high expression of circWSB1 and WSB1 is correlated with poorer clinical prognosis and pathological grading. Conclusions: circWSB1 diminishes the inhibitory impact of miR-182-5p on WSB1, and increases WSB1 expression, thereafter promotes ccRCC development. Our findings provide a promising predictive biomarker and therapeutic target for ccRCC. Citation Format: Guyu Tang, Jing Liu, Xiaomei Gao, Wei Tang, Jiaxian Chen, Menghai Wu, Ye Zhang, Yi Cai, Lin Qi. circWSB1 promotes tumor progression in ccRCC via circWSB1/miR-182-5p/WSB1 axis [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C088.