Circular RNA CircNOLC1, Upregulated by NF-KappaB, Promotes the Progression of Prostate Cancer via miR-647/PAQR4 Axis

<jats:sec><jats:title>Background</jats:title><jats:p>CircRNAs recently have shown critical roles in tumor biology. However, their roles in prostate cancer (PCa) remains largely unclear.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>CircRNA microarrays were performed in immortal prostate cell line RWPE1 and PCa cell lines as DU145, PC3, LNCaP, C4-2, and 22RV1. Combined with upregulated circRNAs in PCa tissues, circNOLC1 expression was validated in PCa cells and tissues <jats:italic>via</jats:italic> qRT-PCR and FISH. Sanger sequencing, actinomycin D, gDNA, and cDNA, RNase R assays were used to assess the circular characteristics of circNOLC1. CCK-8, colony formation, transwell migration assays, and mice xenograft models were conducted to evaluate the functions of PCa cells after circNOLC1 knockdown and overexpression. RNA pulldown, luciferase reporter assay, FISH (fluorescence <jats:italic>in situ</jats:italic> hybridization), and CHIP were utilized to illustrate the further mechanisms of circNOLC1.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Our research indicated that circNOLC1 was overexpressed in PCa cells and tissues, and circNOLC1 was more stable than linear NOLC1 mRNA. CircNOLC1 promoted PCa cells proliferation and migration <jats:italic>in vitro</jats:italic> and <jats:italic>vivo</jats:italic>. Additionally, we found that circNOLC1 could upregulate PAQR4 expression by sponging miR-647, leading to the activation of PI3K/Akt pathway. Moreover, NF-kappaB was identified to bind to the NOLC1 promoter sites and upregulated both NOLC1 and circNOLC1 expression.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>CircNOLC1, elevated by transcription factor NF-kappaB, promotes PCa progression <jats:italic>via</jats:italic> a miR-647/PAQR4 axis, and circNOLC1 is a potential biomarker and target for PCa treatment.</jats:p></jats:sec>