circARL15 Plays a Critical Role in Intervertebral Disc Degeneration by Modulating miR-431-5p/DISC1

Abstract

Background: Intervertebral disk degeneration (IDD) is a serious public health problem associated with genetic and environmental factors. However, the pathogenic factors involved and the pathological mechanism of this disease still remain enigmatic. Methods: The associated microarray was downloaded and further analyzed using statistical software R. The competing endogenous RNA (ceRNA) co-expression network was constructed to measure the meaningful correlated expression of differentially expressed genes. We further measured the expression of circARL15/miR-431-5p/DISC1 in IDD tissues. Cell proliferation and apoptosis were detected in NP cells transfected with a circARL15 overexpression plasmid and miR-431-5p mimics. The expression of DISC1 was detected by immunohistochemistry and Western blot analysis. Results: Within the ceRNA network, circARL15 is the most differentially expressed circular RNA. circARL15 was down-regulated in IDD and was negatively correlated with miR-431-5p and positively associated with DISC1. miR-431-5p was found to bind directly to circARL15 and DISC1. circARL15 inhibited nucleus pulposus cell apoptosis but promoted nucleus pulposus cell proliferation by targeting the miR-431-5p/DISC1 signaling pathway. Conclusion: circARL15/miR-431-5p/DISC1 is involved in the pathogenesis of IDD, which might be helpful in determining the diagnostic biomarkers and providing potential therapeutic targets for patients with IDD.