Expression and clinical significance of microRNA 146a in peripheral blood mononuclear cells from type 2 diabetic neuropathy patients

MicroRNAs (miRNAs) have emerged as important regulatory factors in the development of diabetes and its chronic complications. We investigated the expression levels and clinical significance of miRNA 146a (miR-146a) in peripheral blood mononuclear cells (PBMCs) of type 2 diabetes (T2D) patients with or without diabetic peripheral neuropathy (DPN) and healthy controls. SYBR quantitative real-time PCR (qRT-PCR) was used to examine expression levels of miR-146a in PBMCs of 37 T2D patients with non-diabetic peripheral neuropathy (NDPN), 44 T2D patients with DPN, and 34 healthy controls. Receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic value of miR-146a expression in PBMCs for DPN patients. The correlation between miR-146a expression and clinical parameters was analyzed. Expression levels of miR-146a in the NDPN group decreased slightly compared with those in the healthy control group (p < 0.05), and the levels further decreased in the DPN group (p < 0.05). The area under the ROC curve was 0.807 (95% CI = 0.720-0.893), and the sensitivity for DPN diagnosis and specific degrees were 85.3% and 75.1%, respectively. Expression levels of miR-146a negatively correlated with tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) but were not related to other clinical parameters. This study revealed that decreased miR-146a expression from PBMCs is associated with DPN, suggesting a mechanism wherein decreased miR-146a expression activates the NF-KB target genes, leading to increased TNF-alpha and IL-6 production. This may serve as a novel molecular biomarker for early diagnosis and disease severity evaluation of DPN.