Aberrant miR-410-5p expression occurs in human lumbar intervertebral disk degeneration and improves nucleus pulposus cell degeneration by targeting AIFM1.

Lumbar intervertebral disk degeneration (IDD) is a degenerative disease characterized by nucleus pulposus cells (NPCs) senescence and dysfunction, and microRNAs (miRNAs) play crucial regulatory roles in its pathogenesis. However, the role of miR-410-5p in IDD remains unclear. To investigate the expression pattern and diagnostic value of miR-410-5p in IDD, and explore its molecular mechanism in regulating NPCs degeneration by targeting AIFM1. Bioinformatics analysis was performed using the GEO dataset GSE116726 to screen differentially expressed miRNAs. Clinical samples from 95 IDD patients and 81 healthy controls were collected to detect serum miR-410-5p and AIFM1 expression by RT-qPCR, and their diagnostic value was evaluated by ROC curve and logistic regression. A TNF-α-induced NPCs senescence model was constructed, and the regulatory relationship between miR-410-5p and AIFM1 was verified by dual-luciferase reporter assay. The effects of miR-410-5p and AIFM1 on NPCs senescence, inflammation, and ECM metabolism were detected by SA-β-gal staining, ELISA, and RT-qPCR. MiR-410-5p was significantly downregulated in IDD patients and TNF-α-induced NPCs, and it has good diagnostic value for IDD. MiR-410-5p directly targeted AIFM1, and their expressions were negatively correlated. MiR-410-5p overexpression reduced senescence markers (p16, p21, SA-β-gal activity), inflammatory factors (IL-1β and IL-6), and promoted ECM-related genes (COL2A1, ACAN), while AIFM1 overexpression reversed these effects. MiR-410-5p is downregulated in IDD and serves as a potential diagnostic marker. It alleviates TNF-α-induced NPCs senescence, inflammation, and ECM degradation by targeting AIFM1, providing a new target for IDD therapy.