Urinary Exosomal miR-17-5p Accelerates Bladder Cancer Invasion by Repressing its Target Gene ARID4B and Regulating the Immune Microenvironment

Abstract

BackgroundUrothelial bladder cancer (BCa) is a common malignant tumor of the urinary system. It has been identified that exosomal miRNAs contribute to the development of BCa. However, its significance and mechanism in the malignant biological behavior of BCa remain unclear. In this study, the influence of exosomal miRNAs on BCa progression was investigated. MethodsHigh-throughput sequencing was conducted to analyze the microRNA-expression profile in urinary exosomes to screen out the key miRNA of muscle-invasive bladder cancer (MIBC). Then, candidate miRNA expression was verified and validated in urinary exosomes and tissue samples. To address the potential role of the candidate miRNA, we overexpressed and knocked down the candidate miRNA and explored its activity in BCa cell lines. Furthermore, the target gene of the selected miRNA was predicted and validated. ResultsThe expression profile of miRNAs revealed increased expression of miR-17-5p in MIBC urinary exosomes, and this was later confirmed in urinary exosomes and tissue samples. Cell function studies revealed that exosomal miR-17-5p significantly promoted the growth and invasion of BCa cells. Bioinformatics and luciferase experiments demonstrated that the ARID4B mRNA 3′ UTR might be the binding site for miR-17-5p. Low ARID4B levels were linked to high-grade BCa patients and were associated with a better prognosis. ConclusionElevated miR-17-5p contributes to BCa progression by targeting ARID4B and influencing the immune system. Based on these findings, miR-17-5p has the potential to be a new therapeutic target for the treatment of BCa.