LncRNA PTGS2 regulates islet β-cell function through the miR-146a-5p/RBP4 axis and its diagnostic value in type 2 diabetes mellitus.

OBJECTIVE To investigate the effect of long non-coding RNA (LncRNA) PTGS2 on islet β-cell function via the miR-146a-5p/Retinol binding protein 4 (RBP4) axis and its diagnostic value in type 2 diabetes mellitus (T2DM). METHODS The Gene Expression Omnibus (GEO) was analyzed and LncRNA PTGS2 was identified as a potential regulator of T2DM. Mouse pancreatic β cell INS-1 cells were cultured with high glucose, and the relative expression of LncRNA PTGS2 in the serum of T2DM patients and INS-1 cells was detected by Fluorescence Quantitative PCR (qRT-PCR) and its diagnostic value for T2DM was analyzed. The PTGS2/miR-146a-5p/RBP4 axis in INS-1 cells was intervened to observe the changes in cell function. The proliferation of INS-1 cells was detected by CCK8, and the level of insulin secretion was detected by enzyme linked immunosorbent assay (ELISA). The regulatory relationship among LncRNA PTGS2, miR-146a-5p and RBP4 was determined by dual-luciferase reporter assay. RESULTS The expression of LncRNA PTGS2 in the serum of T2DM patients increased, and the expression of LncRNA PTGS2 was positively correlated with the fasting blood glucose level of patients (R=0.306, P<0.05). Knockdown of LncRNA PTGS2 could promote the proliferation and insulin secretion of INS-1 cells, while overexpression of LncRNA PTGS2 showed the opposite results (all P<0.05). Knockdown of LncRNA PTGS2 could up-regulate the expression of miR-146a-5p. Overexpression of LncRNA PTGS2 inhibited the proliferation and insulin secretion of INS-1 cells, while miR-146a-5p could partially reverse this effect. RBP4 has been identified as a downstream target gene of miR-146a-5p. Overexpression of miR-146a-5p could inhibit the expression of RBP4, which was positively correlated withLncRNA PTGS2 regulation. The effect of RBP4 on INS-1 cells was the same as that of LncRNA PTGS2. CONCLUSION LncRNA PTGS2 can damage islet β-cell function by regulation of miR-146a-5p and up-regulation of RBP4. LncRNA PTGS2 has potential value in the diagnosis of T2DM.