LncRNA TRPC7-AS1 regulates nucleus pulposus cellular senescence and ECM synthesis via competing with HPN for miR-4769-5p binding.

Intervertebral disc (IVD) degeneration (IDD) is identified as an abnormal, cell-mediated, age-dependent and genetics-dependent molecular degeneration process in which NPCs (nucleus pulposus cells) senesce and the balance of ECM (extracellular matrix) synthesis and catabolism is disrupted. Increasing evidence reveals that IDD can be modulated by genetic factors, including non-coding RNAs. In the present study, we downloaded non-coding RNA profiling (GSE56081 and GSE63492) and performed GO annotation and enrichment analysis and association analyses on differentially-expressed genes. LncRNA TRPC7-AS1, miR-4769-5p, and Hepsin (HPN) may form a lncRNA-miRNA-mRNA network that can regulate NPC proliferation, senescence and ECM in IDD. LncRNA TRPC7-AS1 directly targets miR-4769-5p while miR-4769-5p directly targets HPN 3'UTR. miR-4769-5p overexpression inhibited HPN expression, suppressed NPC senescence, promoted NPC viability, and promoted ECM synthesis. The effect of TRPC7-AS1 silence on NPCs was similar as miR-4769-5p overexpression while the effect of HPN overexpression was opposite to miR-4769-5p overexpression. miR-4769-5p suppression or HPN overexpression could significantly attenuate the effect of TRPC7-AS1 silence. LncRNA TRPC7-AS1 relieves miR-4769-5p-induced inhibition on HPN via acting as a ceRNA, thus regulating NPC viability, senescence, and ECM synthesis. In summary, we regard lncRNA-miRNA-mRNA modulation as a new potent target for IDD treatment.