miR-34a-5p Predicts the Risk of Diabetic Neuropathic Pain and Mediates Neuroinflammation in Microglia via Targeting ENPP3.

INTRODUCTION The pathogenesis of diabetic neuropathic pain (DNP) is complex involving various processes, which need exploring reliable biomarkers for its early detection and severity prediction. METHODS Study enrolled 181 patients diagnosed with diabetes, among which 74 patients developed DNP. Serum miR-34a-5p levels were compared between DNP patients and non-DNP patients by polymerase chain reaction (PCR), and the potential of miR-34a-5p in predicting the risk and discriminating patients with DNP was evaluated. The regulatory effect of miR-34a-5p on the inflammation, proliferation, and polarization of microglia was evaluated in HMC3 cells treated with high glucose. RESULTS Upregulated miR-34a-5p was identified as a risk factor and discriminated DNP patients miR-34a-5p was positively correlated with the levels of triglyceride (r = 0.797), fasting blood glucose (r = 0.840), and glycated hemoglobin (r = 0.894) of DNP patients. In HMC3 cells, the high-glucose-induced inflammation, promoted cell growth and caused polarization. The knockdown of miR-34a-5p showed the significant protective effect of microglia activation by high glucose, which was reversed by silencing ENPP3. DISCUSSION miR-34a-5p served as a biomarker for the prediction and early detection of DNP and mediated microglia inflammation caused by DNP via modulating ENPP3.