circSOBP Inhibits Bladder Cancer Proliferation and Metastasis by Regulating the miR-200a-3p/PTEN Axis and Participating in the Immune Response

Abstract

A growing body of evidence shows that circular RNAs (circRNAs) participate in tumor growth and metastasis and also play crucial roles in the treatment and prognosis of various cancers. In this article, we identified a novel circRNA, circSOBP (has_circ_0001633), based on the results of high-throughput RNA sequencing, and its expression was subsequently validated via quantitative reverse transcription polymerase chain reaction in bladder cancer (BCa) tissues and cell lines. The association between circSOBP expression and the clinicopathologic features and prognosis of 56 recruited BCa patients was then analyzed, and the biological roles of circSOBP were assessed by in vitro cloning formation, wound healing, transwell, CCK-8, and in vivo xenograft mouse models. Next, the competitive endogenous RNA mechanism was explored through fluorescence in situ hybridization, RNA pull-down, luciferase reporter, bioinformatics analysis, and rescue experiments. Western blot and immunohistochemistry detected the expression of downstream mRNA, and we were able to determine that circSOBP was downregulated in BCa tissues and cell lines and that lower circSOBP expression was associated with more advanced pathological stage, larger tumor size, and poorer overall survival with BCa patients. Overexpressed circSOBP suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, competitive interactions between circSOBP and miR-200a-3p enhanced target gene PTEN expression. In addition, we found a significant correlation between higher expression of circSOBP in BCa patients after immunotherapy than before and a better treatment outcome, indicating that circSOBP might regulate the programmed death 1/programmed death ligand 1 pathway. Overall, circSOBP inhibits BCa tumorigenesis and metastasis by a novel miR-200a-3p/PTEN axis, which makes it an excellent biomarker and therapeutic target for treating BCa.