AUTHOR=Wang Hanbang , Zhu Yakun , Cao Le , Guo Ziming , Sun Kai , Qiu Wangbao , Fan Haitao TITLE=circARL15 Plays a Critical Role in Intervertebral Disc Degeneration by Modulating miR-431-5p/DISC1 JOURNAL=Frontiers in Genetics VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.669598 DOI=10.3389/fgene.2021.669598 ISSN=1664-8021 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.