MiR-766-3P promotes degenerative lumbar disc disease by regulating SIRT6 to aggravate the inflammatory response of human nucleus pulposus cells

Abstract Background Lumbar degenerative disc disease (LDD) is a disabling condition which was associated with progressive degeneration of the intervertebral discs. The miR-766-3p and its modulation of SIRT6 remains unclear in LDD. Purpose This study aims to explored the regulated function of miR-766-3p and SIRT6 during LDD. Methods Human nucleus pulposus cells (HNPCs) were treated with lipopolysaccharide (LPS) to construct a model of LDD to simulate inflammatory conditions. RT-qPCR and ELISA assays were employed to measure the expression of miR-766-3p and SIRT6. Additionally, we evaluated the levels of TNF‑α, IL‑1β, IL‑6, aggrecan, and collagen II by ELISA. Dual-luciferase reporter assays validated direct targeting between miR-766-3p and SIRT6. Results We observed that miR-766-3p was upregulated in LDD patients, and SIRT6 was downregulated. It is consistent with the changes in LPS-induced HNPCs. Additionally, when we inhibited the miR-766-3p and overexpressed SIRT6, inflammatory cytokines decreased, whereas aggrecan and collagen II increased. Moreover, the inhibition of miR-766-3p increased SIRT6, which was decreased by LPS. And the binding relationship between miR-766-3p and SIRT6 was confirmed by luciferase activity. MiR-766-3p mimic reversed the effects of elevated SIRT6 expression. Conclusion The findings identify the miR-766-p/SIRT6 axis as a critical regulator mediating inflammatory responses and driving extracellular matrix degradation during LDD. Targeting this molecular pathway would offer novel therapeutic strategies for mitigating tissue damage of LDD.