Inhibition of intervertebral disc disease progression via the circPKNOX1–miR-370-3p–KIAA0355 axis

The molecular mechanism underlying the development of intervertebral disc disease (IVDD) is not completely understood. Circular RNAs (circRNAs) play a significant role in the occurrence and development of various diseases, and studies have shown that circPKNOX1 is involved in the compensatory response of extracellular matrix synthesis and secretion of the nucleus pulposus (NP) cells. However, the mechanism through which circRNAs regulate IVDD progression remains unclear; therefore, in this study, we explored the significance of circPKNOX1 in IVDD. The expression of circRNAs in NP cells of normal and degenerative patients was detected using microarray analysis, and the role of circPKNOX1 in IVDD was confirmed using RT-qPCR. The interaction networks of circRNAs, miRNAs, and miRNA target genes were detected using bioinformatics analysis, RNA fluorescence in situ hybridization, and immunofluorescence analysis. We found that the expression of circPKNOX1 decreased in IVDD cells. The expression of circPKNOX1 in NP cells, observed using RT-qPCR and western blotting, was consistent with that observed using array screening. Overexpression of circPKNOX1 increased the expression of collagen II, aggrecan, and SOX9 and decreased that of ADAMTS4, ADAMTS-5, MMP3, and MMP13. We further demonstrated that circPKNOX1 played the role of a sponge by competitively binding miR-370-3p to reverse the inhibition of KIAA0355 expression. Our findings indicated that circPKNOX1 affected the progression of IVDD by regulating the expression of KIAA0355 via miR-370-3p. Therefore, circPKNOX1-based therapy may serve as an effective IVDD treatment strategy.