The clinical role of lncRNA PRKG1-AS1 in lumbar disc degeneration and its mechanism in regulating inflammation and ferroptosis via miR-218-5p.

BACKGROUND

Lumbar disc degeneration (LDD) is a common spinal disorder that predisposes patients to lumbar disc herniation (LDH) and causes chronic low back pain. Its pathogenesis remains incompletely understood. This study investigated the clinical relevance of PRKG1-AS1 in LDD and explored its regulation of LDD progression through miR-218-5p, providing experimental support for LDD targeted treatment.

METHODS

This study enrolled 128 LDD patients and 102 healthy individuals to measure serum levels of PRKG1-AS1 and analyze its associations with clinical parameters. A degeneration model of human nucleus pulposus cells (hNPCs) was established using TNF-α induction. The effects of PRKG1-AS1 on cell proliferation, metabolic balance, ferroptosis, inflammation, and oxidative stress were assessed through transfection experiments. Additionally, dual-luciferase reporter assays confirmed the targeted binding interactions.

RESULTS

Serum PRKG1-AS1 showed strong diagnostic value for LDD. Its expression was closely related to disease severity and patient functional status, making it an independent risk factor for progression from LDD to LDH. Overexpressing PRKG1-AS1 significantly improved the TNF-α-induced degenerative phenotype, enhanced hNPCs proliferation, restored metabolic balance, reduced ferroptosis, and alleviated inflammation and oxidative stress damage. Dual-luciferase assays confirmed that PRKG1-AS1 directly binds to miR-218-5p, and miR-218-5p targets CUL3. PRKG1-AS1 exerted a protective effect in LDD progression via the miR-218-5p/CUL3 axis.

CONCLUSION

Serum PRKG1-AS1 may serve as a promising biomarker for early detection and prediction of LDD progression. It modulates inflammation and ferroptosis in nucleus pulposus cells through the PRKG1-AS1/miR-218-5p/CUL3 axis, thereby inhibiting the LDD development.