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August 30, 2026European Neurology

Downregulation of miR-33a-5p regulates TNF-α/NF-κB signaling and is associated with reduced diabetic neuropathic pain through targeting SIRT6

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Authors

WLWenju LiYLYimei LiYWYongxin Wang

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Overview

Translational study demonstrates that miR-33a-5p promotes neuroinflammation via SIRT6 in diabetic neuropathic pain, highlighting a therapeutic target.

Key Points

  • To elucidate how miR-33a-5p and SIRT6 regulate TNF-α/NF-κB signaling and contribute to neuroinflammation in diabetic neuropathic pain.
  • Measured serum miR-33a-5p levels via qPCR in diabetic patients with and without diabetic neuropathic pain, assessing diagnostic utility via ROC analysis.
  • Established a high-glucose HMC3 microglial cell culture model to quantify oxidative stress, cell proliferation, and TNF-α and NF-κB expression by ELISA.
  • Identified the targeting relationship between miR-33a-5p and SIRT6 using dual-luciferase reporter assays and functional perturbation experiments.
  • Serum miR-33a-5p was significantly increased in patients with diabetic neuropathic pain (p < 0.001), correlated positively with HbA1c (p < 0.001), and demonstrated diagnostic utility (AUC = 0.906, p < 0.001).
  • High-glucose exposure in microglia triggered significant elevations in miR-33a-5p (p < 0.01), NF-κB (p < 0.001), TNF-α (p < 0.001), and oxidative stress (p < 0.001).
  • Direct targeting of SIRT6 by miR-33a-5p activated the NF-κB/TNF-α/p38MAPK pathway, whereas miR-33a-5p inhibition or SIRT6 overexpression significantly reduced microglial activation and neuroinflammation (p < 0.01).

Cite This Study

Li et al. (2026) studied this question.

synapsesocial.com/papers/6a93f0ce6c1a8fb52e79d4b2https://doi.org/10.1159/000552973
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1miR-34a-5p Predicts the Risk of Diabetic Neuropathic Pain and Mediates Neuroinflammation in Microglia via Targeting ENPP32024 · 4 citations
  2. 2PRMT6 inhibition or deficiency attenuates diabetic neuropathic pain in male mice and is associated with reduced spinal neuroinflammation, microgliosis, and altered p53-p21 signaling2026
  3. 3<scp>MiR</scp> ‐210‐3p is upregulated in diabetic peripheral neuropathy and may be involved in the progression of the disease by targeting brain‐derived neurotrophic factor2026
  4. 4Hyperglycemia‐induced Sirt3 downregulation increases microglial aerobic glycolysis and inflammation in diabetic neuropathic pain pathogenesis2024 · 10 citations
  5. 5<scp>miR</scp> ‐27a‐3p Upregulation and Netrin‐1 Deficiency Drive Inflammatory Responses and Nerve Degeneration in Patients With Diabetes2025