microRNA-155-3p attenuates intervertebral disc degeneration via inhibition of KDM3A and HIF1α

Abstract

Objective: Intervertebral disc degeneration (IDD) is a key element resulting in low back pain, but the mechanisms underlying IDD remain largely unknown. The purpose of the study was to investigate the influence of microRNA-155-3p (miR-155-3p) on proliferation and autophagy of nucleus pulposus (NP) cells in IDD with the involvement of hypoxia-inducible factor 1 α (HIF1α)/histone lysine demethylase 3A (KDM3A) axis.

Methods: IDD NP tissues of patients with lumbar disc herniation and traumatic intervertebral disc NP tissues from patients with traumatic lumbar fracture were collected. Apoptosis in NP tissues was observed, and autophagy marker proteins in NP tissues were detected. NP cells in IDD were transfected with miR-155-3p mimic or KDM3A-siRNA to explore their roles in cell proliferation, autophagy and apoptosis. MiR-155-3p, KDM3A and HIF1α expression in NP tissues and cells were detected.

Results: Decreased miR-155-3p, and elevated HIF1α and KDM3A were presented in NP tissues and cells of IDD. Elevated miR-155-3p or silenced KDM3A promoted the proliferation and autophagy, and inhibited the apoptosis of NP cells of IDD. Moreover, elevated miR-155-3p decreased KDM3A and HIF1α expression, while silenced KDM3A decreased HIF1α expression in NP cells with IDD.

Conclusion: The study concludes that up-regulated miR-155-3p or silenced KDM3A promotes the proliferation, autophagy, and restrains the apoptosis of NP cells of IDD via inhibition of HIF1α, which may be a promising approach for the treatment of IDD.

Keywords: Apoptosis; Autophagy; Hypoxia-inducible factor 1 α; Intervertebral disc degeneration; Lysine demethylase 3A; MicroRNA-155-3p; Nucleus pulposus cells; Proliferation.