MicroRNA‑25‑3p regulates human nucleus pulposus cell proliferation and apoptosis in intervertebral disc degeneration by targeting Bim

Abstract

Intervertebral disc degeneration (IDD) is a degenerative disease of the spine originating from the intervertebral disc. MicroRNAs (miRNAs or miRs) are a group of endogenous small non-coding RNAs that act on target genes and play a critical role in numerous biological processes. However, the underlying mechanism of miR-25-3p in IDD remains unclear. Therefore, the present study aimed to explore the role of miR-25-3p in the pathogenesis of IDD. The results demonstrated that miR-25-3p was downregulated in rat degenerative nucleus pulposus (NP) cells and that Bcl-2 interacting mediator of cell death (Bim) was a direct target of miR-25-3p. Next, to investigate the effect of miR-25-3p on normal NP cell proliferation and apoptosis, NP cells were transfected with an miR-25-3p inhibitor, a negative control of miR-25-3p inhibitor, miR-25-3p inhibitor + control-small interference RNA (siRNA) or miR-25-3p inhibitor + Bim-siRNA for 48 h and cell proliferation and apoptosis were then analyzed. The results demonstrated that the miR-25-3p inhibitor could decrease NP cell proliferation and induce cell apoptosis, and these effects were reversed by Bim-siRNA. In addition, an in vitro cell model of IDD was established by subjecting NP cells to 10 ng/ml interleukin (IL)-1β for 24 h. Further experiments suggested that IL-1β treatment induced a reduction in NP cell proliferation and an increase in cell apoptosis, which were prevented by the miR-25-3p mimic. All the effects of miR-25-3p mimic on IL-1β-treated NP cells were significantly reversed by Bim upregulation. These findings suggested that miR-25-3p may be a novel therapeutic target for IDD prevention.