miR-4632-5p Alleviates Lumbar Disc Degeneration by Targeting MAP3K11: A Novel Role in Mitigating Nucleus Pulposus...

Lumbar disc degeneration (LDD) is a major cause of chronic low back pain, and current treatments only provide symptomatic relief. This study aimed to investigate the role of miR-4632-5p and its target MAP3K11 in the pathogenesis of LDD. Bioinformatics analysis was used to predict target genes of miR-4632-5p. LDD tissues (n=22) and normal intervertebral disc (IVD) tissues (n=19) were collected to detect the expression of miR-4632-5p and MAP3K11 by RT-qPCR. A dual-luciferase reporter assay validated their direct interaction. In vitro, TNF-α-induced human nucleus pulposus cells (HNPCs) degeneration models were used to evaluate the effects of miR-4632-5p/MAP3K11 on cell viability, apoptosis, oxidative stress, and inflammatory cytokine secretion via CCK-8, flow cytometry, and ELISA. miR-4632-5p was significantly downregulated in LDD tissues, whereas MAP3K11 was upregulated (P<0.0001), and their expression showed a strong negative correlation (r=-0.82, P<0.0001). miR-4632-5p targeted the 3'UTR of MAP3K11, reducing dual luciferase activity by 35.9% (P<0.001). Overexpression of miR-4632-5p alleviated TNF-α-induced HNPC injury by enhancing cell viability, reducing the apoptotic rate by approximately 26%, improving redox homeostasis (lower MDA/ROS, higher SOD), and reduced the secretion of pro-inflammatory cytokines (IL-6, IL-1β, IL-8, IL-17) by 19%-25% (all P<0.001). These effects were abolished by concurrent MAP3K11 overexpression. Western blotting confirmed that miR-4632-5p reduced MAP3K11 protein levels and inhibited TNF-α-induced NF-κB p65 phosphorylation. In summary, the dysregulated expression of miR-4632-5p and MAP3K11 suggests their potential as exploratory biomarker candidates for LDD, and the miR-4632-5p/MAP3K11 axis represents a preliminary candidate strategy for LDD treatment.