A MicroRNA Signature in Gestational Diabetes Mellitus Associated with Risk of Macrosomia.

BACKGROUND/AIMS MicroRNA (miRNA) is a small non-coding RNA molecule that functions in regulation of gene expression by targeting mRNA to affect its stability and/or translation. The aim of this study was to evaluate the miRNAs involvement in gestational diabetes mellitus (GDM), a well known risk factor for fetal overgrowth. METHODS Differential microRNA expression in placental tissues of normal controls and women with GDM were identified by miRNA micorarray analysis and further confirmed by quantitative real-time PCR (qRT-PCR) on an independent set of normal and GDM placental tissues. Target genes of microRNAs were bioinformatically predicted and verified in vitro by Western blotting. RESULTS Our results uncovered 9 miRNAs that were significantly deregulated in GDM samples: miR-508-3p was up-regulated and miR-27a, miR-9, miR-137, miR-92a, miR-33a, miR-30d, miR-362-5p and miR-502-5p were down-regulated. Bioinformatic approaches revealed that the microRNAs signature identifies gene targets involved in EGFR (epidermal growth factor receptor)-PI3K (phosphoinositide 3-Kinase)-Akt (also known as protein kinase B) pathway, a signal cascade which plays important roles in placental development and fetal growth. We found that the protein levels of EGFR, PI3K and phospho-Akt were up-regulated and PIKfyve (a FYVE finger-containing phosphoinositide kinase), a negative regulator of EGFR signaling, was down-regulated significantly in GDM tissues. We also confirmed PIKfyve was a direct target of miR-508-3p. CONCLUSION Our data identified a miRNA signature involvement in GDM which may contribute to macrosomia through enhancing EGFR signaling.