miR-199a-3p is involved in the pathogenesis and progression of diabetic neuropathy through downregulation of SerpinE2

The present study aimed to investigate the expression status of miRNA‑199a‑3p in patients with diabetic neuropathy (DN) and the mechanism by which this miRNA is involved in the genesis of DN. The expression of miRNA‑199a‑3p in plasma of peripheral blood was compared between patients with diabetes and a family history of diabetes and control volunteers by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR); in 60 diabetes patients, 45 (75%) demosntrated upregulated miR‑199a‑3p expression compared with control volunteer plasma. RT‑qPCR was also used to detect miRNA‑199a‑3p expression in paired lower limb skin tissues from 30 patients with DN and 20 control volunteers; miR‑199a‑3p expression in patients with DN was significantly higher than in the control group. Next miR‑199a‑3p expression levels were evaluated with respect to the clinic‑pathological parameters of diabetes; increased expression of miR‑199a‑3p was significantly associated with increased disease duration (P=0.041), glycated hemoglobin (HbA1C) levels (P=0.033), and fibrinogen levels (P=0.003). Finally, the effects on downstream mRNA expression levels were investigated as a result of manipulating miR‑199a‑3p levels. miR‑199a‑3p overexpression inhibited the expression of the extracellular serine protease inhibitor E2 (SerpinE2). Therefore, it may be hypothesized that miR‑199a‑3p can induce DN via promoting coagulation in skin peripheral circulation, through the downregulation of SerpinE2. The present findings suggested that miR‑199a‑3p may have potential as a novel therapeutic target for the treatment of patients with DN.