24 Correlation between the expression of proinflammatory cytokine genes and immunomodulatory microRNAs miR-27a, miR-222 and miR-340 in peripheral blood mononuclear cells of women with gestational diabetes

Abstract

Continuous low-level inflammation (IFM) is a major contributory factor to development of severe pregnancy complications associated with gestational diabetes mellitus (GDM). Presence of IFM throughout the hyperglycemic pregnancy associates with disturbances in microRNA-related mechanisms, while inflammatory pathway-related genes are known targets of microRNAs dysregulated in GDM. Our aim was to evaluate the correlation between the expression of GDMrelated microRNAs (miR-27a, miR-222 and miR-340) and mRNA encoding proinflammatory cytokines IL-1β, IL-8, TNFα and IL6 in peripheral blood mononuclear cells (PBMCs) from women with GDM and healthy controls. PBMCs were isolated from blood samples during pregnancy weeks 24-30 (n=50 per group). Relative quantification of relevant microRNAs and mRNAs was conducted by quantitative real-time PCR, while Pearson correlation test was used for statistical evaluation of the obtained results. The expression of all three selected microRNAs showed negative correlation with the level of IL-8 and TNFα mRNA in PBMCs of GDM patients (negative r ranging 0.318–0.375), while such findings lacked for the control group. Additionally, miR-340 demonstrated correlation with the expression of IL-1β (r=-0.333). None of the microRNAs correlated with the expression of IL-6, which was the only mRNA with a statistically significant upregulation in GDM, compared to controls. The presented results illustrate the relation between the dysregulation of GDM-associated microRNAs and the expression of immune system modulators in GDM. The direction of correlation was negative and in accordance with the hypothesised regulatory mechanisms. Additional findings on circulatory levels of proinflammatory cytokines are required for further interpretation of IFM-related properties of selected microRNAs.BeCELS 2025: Belgrade Conference for Early-Career Life Scientists, taking place on Friday, September 5, 2025, at the Institute of Molecular Genetics and Genetic Engineering (IMGGE) in Belgrad