Circ_0044516 Enriches the Level of SARM1 as a miR-330-5p Sponge to Regulate Cell Malignant Behaviors and Tumorigenesis of Prostate Cancer.

Abstract

Prostate cancer (PCa) is one of the most common and deadly cancers in men. The dysregulated circular RNAs (circRNAs) are involved in the development of various cancers, including PCa. The purpose of this study was to construct a circRNA-microRNA (miRNA)-mRNA network to explain the function of circ_0044516 in PCa. The expression analysis of circ_0044516, miR-330-5p, and sterile alpha and TIR motif-containing 1 (SARM1) was performed using real-time quantitative polymerase chain reaction, and the protein level of SARM1 was detected by western blot. The interaction between miR-330-5p and circ_0044516 or SARM1 obtained by bioinformatics prediction was verified by dual-luciferase reporter assay or RNA immunoprecipitation assay. For functional studies, cell proliferation was assessed by cell viability and colony formation ability using cell counting kit-8 assay and colony formation assay. Cell migration and invasion were studied using transwell assay. Cell apoptosis and cell cycle were investigated using flow cytometry assay. The tumorigenicity of circ_0044516 was tested by animal study. Circ_0044516 and SARM1 were highly expressed, while miR-330-5p was rarely expressed in PCa tissues and cells. Circ_0044516 acted as a miR-330-5p sponge to block miR-330-5p expression, and circ_0044516 knockdown suppressed PCa cell proliferation, migration, invasion, and cycle progression by enriching miR-330-5p. SARM1 was a target of miR-330-5p, and miR-330-5p restoration also inhibited PCa cell proliferation, migration, invasion, and cycle progression by degrading SARM1. Moreover, circ_0044516 deficiency blocked tumor growth in vivo by regulating the miR-330-5p/SARM1 axis. Circ_0044516 as a miR-330-5p sponge increases SARM1 expression, thus promoting the malignant development of PCa.