MicroRNA-199a-5p accelerates nucleus pulposus cell apoptosis and IVDD by inhibiting SIRT1-mediated deacetylation of p21

Abstract

Intervertebral disc degeneration (IVDD) is a multifactorial pathological process associated with low back pain in which nucleus pulposus cell senescence is disrupted. Increasing evidence reveals that IVDD can be modulated by microRNAs (miRNAs or miRs). In the current study, we set out to elucidate the role of miR-199a-5p in nucleus pulposus cell apoptosis and IVDD progression. After sample collection, we found highly expressed miR-199a-5p in nucleus pulposus tissues of both patients diagnosed with IVDD and in IVDD rat models. Next, normal and degenerated nucleus pulposus cells were isolated and transfected with miR-199a-5p mimic, miR-199a-5p inhibitor, overexpressed sirtuin 1 (oe-SIRT1), and oe-p21, followed by detection of nucleus pulposus cell apoptosis and proliferation. In addition, the binding of miR-199a-5p and SIRT1, the interaction between p21 and SIRT1, and the regulation of p21 acetylation by SIRT1 were analyzed. We found that miR-199a-5p overexpression promoted nucleus pulposus cell apoptosis and IVDD. Overexpression of SIRT1 countered the effect of miR-199a-5p overexpression, while overexpression of p21 reversed the effect of miR-199a-5p silencing. Also, miR-199a-5p inhibited SIRT1, promoted p21 acetylation, and upregulated p21 expression, thus accelerating nucleus pulposus cell apoptosis and IVDD. Overall, miR-199a-5p promotes nucleus pulposus cell apoptosis and IVDD by suppressing SIRT1-dependent deacetylation of p21.

Keywords

• microRNA-199a-5p
• SIRT1
• p21 deacetylation
• intervertebral disc degeneration
• nucleus pulposus cells