Serum miRNAs are potential biomarkers for the detection of disc degeneration, among which miR-26a-5p suppresses Smad1 to regulate disc homeostasis

Abstract

Disc degeneration is a common clinical condition in which damaged discs cause chronic pain; however, a laboratory diagnosis method for its detection is not available. As circulating miRNAs have potential as biomarkers, their application in disc degeneration has not been explored. Here, we prepared serum miRNAs from a mouse disc degeneration model and performed miRNA-Seq and quantitative PCR to characterize disc degeneration-associated miRNAs. We identified three miRNAs, including miR-26a-5p, miR-122-5p and miR-215-5p, undergoing perturbation during the pathogenesis of disc degeneration. Specifically, the levels of miR-26a-5p in the serum demonstrated steady increases in the model of disc degeneration, compared with those in the pre-injury samples of younger age or compared with normal controls of the same age but without disc degeneration, whereas the miRNAs miR-122-5p and miR-215-5p exhibited lower expression in post-injury samples than in their counterparts without the surgery. Moreover, we found that miR-26a-5p targets Smad1 expression, and Smad1 negatively regulates Vegfa expression in disc cells, and thus, miR-26a-5p promotes disc degeneration. In summary, we established a method that consistently profiles circulating miRNAs and identified multiple miRNAs as promising biomarkers for disc degeneration, among which miR-26a-5p enhances VEGF expression during disc degeneration through targeting Smad1 signalling.

Keywords: miR-26a-5p; Smad1; VEGF; circulating miRNA; disc degeneration; miRNA-Seq.