LncRNA JPX regulates proliferation and apoptosis of nucleus pulposus cells by targeting the miR-18a-5p/HIF-1α/Hippo-YAP pathway

Abstract

With the aggravation of global aging, the rapid rise in the obesity rate, and the increasing number of patients with intervertebral disc degeneration (IDD), the principles and mechanism of this disease remain unclear. This study explored the molecular mechanism of IDD treatment through interactions of the lncRNA-miRNA-mRNA-signaling pathways and the effects on the proliferation and apoptosis of human nucleus pulposus cells (HNPCs) cultured in vitro. Our study revealed that lncRNA JPX is expressed at low levels in HNPCs under normoxic conditions. Luciferase and RNA pull-down assays were used to verify that lncRNA JPX directly bound to miR-18a-5p and influenced HNPC proliferation and apoptosis. Subsequently, a luciferase assay confirmed the direct binding of miR-18a-5p to HIF-1α and demonstrated a negative correlation between miR-18a-5p and HIF-1α. In addition, the HIF-1α antagonist reversed the inhibition of the Hippo-YAP pathway by the miR-18a-5p inhibitor. In conclusion, overexpression of lncRNA JPX upregulated HIF-1α by inhibiting the expression of miR-18a-5p, thereby inhibiting the Hippo-YAP pathway. By inhibiting this pathway, JPX overexpression promoted the proliferation of HNPCs and decreased their apoptosis. Therefore, the lncRNA JPX is a potential new target.

Keywords: HIF-1α; Hippo-YAP signaling Pathway; Nucleus pulposus cells; lncRNA JPX; microRNA-18a-5p.