MiR-502 Suppresses TNF--Induced Nucleus Pulposus Cell Apoptosis by Targeting TARF2.

Intervertebral disc degeneration (IVDD) is a common cause of low back pain. This study is aimed at investigating the role of microRNAs (miRNAs) in regulating human nucleus pulposus (NP) cell injury induced by tumor necrosis factor- (TNF-) in IVDD. In this study, we induced NP cells with 20 ng/mL TNF- in vitro, which promoted the obvious apoptosis of NP cells and the activation of nuclear transcription factor (NF)-B. In contrast, using the specific NF-B inhibitor BAY 11-7082 to treat cells greatly impaired the activation of NF-B and increased the sensitivity of NP cells to TNF--induced apoptosis. Moreover, both TNF- and BAY 11-7082 treatments were associated with marked miRNA dysregulation, with miR-502 being upregulated by TNF- treatment and downregulated by BAY 11-7082 treatment, respectively. And the overexpression of miR-502 enhanced NF-B activation and suppressed apoptosis of human NP cells induced by TNF-, whereas the opposite was observed following miR-502 inhibition. Last, through bioinformatic analyses and luciferase reporter gene experiments, we identified TRAF2, an important activator of NF-B, as a miR-502 target gene. Similarly, siRNA-mediated knockdown of the TRAF2 expression also suppressed TNF--induced apoptosis and enhanced NF-B activation. Our findings provide evidence indicating that miR-502 is a key regulator of apoptosis of human NP cells induced by TNF- by targeting TRAF2 and activating NF-B.