Hsa_Circ_0036763 is a Prognostic Biomarker for Intervertebral Disc Degeneration and Affects the Senescence and Collagen Loss of Nucleus Pulposus Cells via miR-4741/RGSL1

Background: Intervertebral disk degeneration (IDD) is a degenerative disease mainly characterized by intervertebral disk tissue senescence and Collagen loss. The role of hsa_circ_0036763 in IDD remains incompletely understood.

Methods: The clinical value of hsa_circ_0036763 was explored by retrospectively analyzing the serum samples of 120 IDD patients through ROC curve, Kaplan-Meier curve, and COX proportional hazards analysis. The severity of IDD was distinguished through the modified Pfirrmann grading system. The downstream regulatory mechanism (miR-4741/RGSL1) of hsa_circ_0036763 was mined through the miRDB and TargetScan databases, and their targeting relationships were demonstrated by the dual-luciferase reporter and RNA pull-down assays. The IL-1β-induced senescent nucleus pulposus cells (NPCs) were used to evaluate the potential role of hsa_circ_0036763/miR-4741/RGSL1 axis in IDD progression.

Results: Serum hsa_circ_0036763 expression was negatively correlated with the modified Pfirrmann grade of IDD patients (r = -0.675). Its low expression predicted a higher risk of IDD recurrence (HR = 0.252, p = 0.002). Hsa_circ_0036763 sponged miR-4741, thereby relieving its inhibition on RGSL1 expression. Exogenous overexpression of hsa_circ_0036763 alleviated the senescence, Collagen loss, and oxidative stress in IL-1β-induced NPCs, which were reversed by co-transfection of miR-4741 mimics and silencing of RGSL1.

Conclusion: Hsa_circ_0036763 may serve as a prognostic marker for IDD and participates in IDD-related NPC degeneration by regulating miR-4741/RGSL1.