MicroRNA-17-5p acts as a biomarker and regulates mitochondrial dynamics in trophoblasts and endothelial cells by targeting the mitofusins Mfn1/Mfn2 in gestational diabetes mellitus

Abstract

IntroductionGestational diabetes mellitus (GDM) is a metabolic disease that endangers pregnant women and their offspring. Insights into biomarkers and GDM pathogenesis are crucial. Ectopic expression of microRNA-17-5p was found in GDM, but its the diagnostic value and role of miR-17-5p remain unclear.Material and methodsDetection of miRNA microarray and quantitative PCR (qPCR) found that miR-17-5p was significantly increased and positively associated with biochemical indicators of GDM in 30 GDM plasma samples and 28 matched control plasma samples.ResultsThe area under the ROC curve was 0.827 (P < 0.01), which showed good diagnostic potential. Mitochondrial staining showed that compared with controls, trophoblasts exhibited more mitochondrial fusion and endothelial cells exhibited more mitochondrial fission in GDM than these in controls. Western blot and qPCR assays further revealed that expression of the mitofusin Mfn1/Mfn2 was lower in primary endothelial cells from GDM patients, whereas their expression was significantly higher in primary trophoblasts from GDM patients compared with those from controls. Conversely, miR-17-5p expression was higher in primary endothelial cells from GDM patients, whereas their expression was significantly lower in primary trophoblasts from GDM patients compared with those from controls. Bioinformatics and luciferase reporter assays confirmed that both Mfn1 and Mfn2 are targets of miR-17-5p. Last, decreased Mfn1/2 was observed not only to increase the apoptotic rate of primary endothelial cells from GDM, but also to reverse anti-apoptotic effects of miR-17-5p inhibitor.ConclusionsMiR-17-5p regulates Mfn1/Mfn2-mediated mitochondrial dynamics involved in GDM. MiR-17-5p may serve as a promising biomarker and therapeutic target for GDM.