Long Non-Coding RNA Small Nucleolar RNA Host Gene 14 Enhances Pancreatic-β-Cell Function by Sponging MicroRNA-206 and Thereby Upregulating Insulin-Like Growth Factor-1

Abstract

Diabetes mellitus (DM) characterised by pancreatic β-cell dysfunction and insulin resistance is already prevalent worldwide, and the complications of DM increased the mortality of diabetic patients. More and more reports showed that long non-coding RNA (lncRNA) plays key roles in DM, and in this study we explored the effect of long non-coding RNA SNHG14 (SNHG14) in DM. Quantitative reverse transcription PCR (qRT-PCR) was used to analyze the expression of SNHG14 and microRNA (miR)-206 in peripheral blood from 60 pairs of healthy and DM samples. Then the effect of SNHG14 on the insulin secretion of pancreatic β-cells was investigated. Moreover, the effects of SNHG14 on the viability and apoptosis of pancreatic β-cells were determined by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di- phenytetrazoliumromide (MTT) assay and flow cytometry (FCM) respectively using INS-1 cells transfected with SNHG14-plasmid and/or miR-206 mimic. Bioinformatics and Daul luciferase reporter assay were used to confirm the direct target of miR-206. Our data showed that SNHG14 level was decreased but miR-206 was increased significantly in the peripheral blood of DM patients. Furthermore, over-expression of SNHG14 enhanced insulin secretion and cell viability but inhibited apoptosis of pancreatic β-cells, whereas, miR-206 over-expression reversed these effects. In addition, insulin-like growth factor-1 (IGF1) was proved to be regulated by miR-206 negatively and over-expression of SNHG14 increased the expression of IGF1 and IGF1R in pancreatic β-cells. In conclusion, we found that SNHG14 was significantly down-regulated in DM patients, and SNHG14/miR-206/IGF1 may serve as a potential candidate for the clinical target of DM.