Clinical significance and regulatory mechanism of miR-4284 in lumbar intervertebral disc degeneration.

Abstract

Lumbar disc degeneration (LDD) is one of the main causes of low back pain. This study investigates the role of miR-4284 and its target, CYCS, in LDD pathogenesis. Serum levels of miR-4284 and CYCS were measured in 121 LDD patients and 79 healthy controls. The clinical diagnostic and predictive value of miR-4284 was evaluated using ROC curve analysis and logistic regression. Stimulated human nucleus pulposus (NP) cells with LPS and transfected with miR-4284 mimic/inhibitor or CYCS overexpression vector. Cell viability, inflammatory factors (IL-1β, TNF-α), and oxidative stress markers (MDA, T-AOC) were assessed. A luciferase reporter assay confirmed targeting. Western blot analysis was performed to detect the expression of apoptosis-related proteins (Bax, Bcl-2) and mitochondrial function-related proteins (PGC-1α, SOD2). In LDD patients, serum miR-4284 expression was significantly downregulated (P < 0.001) and exhibited good diagnostic value (AUC = 0.831). miR-4284 might serve as a protective factor for LDD (OR = 0.100), showing negative correlations with Pfirrmann grading, ODI, and VAS scores (P < 0.001). Luciferase assays confirmed that CYCS was a direct target of miR-4284. In LPS-stimulated NP cells, miR-4284 overexpression alleviated inflammation and oxidative stress while enhancing cell viability. Concurrently, overexpression of CYCS not only completely reversed the protective effects mediated by miR-4284 but also exacerbated cellular apoptosis and mitochondrial dysfunction, thereby synergistically promoting the pathological progression of LDD. miR-4284 is significantly decreased in LDD and may serve as a protective biomarker. By targeting CYCS, it alleviates inflammation and oxidative stress, inhibits apoptosis, and mitigates mitochondrial dysfunction in NP cells, thereby potentially delaying LDD progression.