Micro-RNAs Let7e and 126 in Plasma as Markers of Metabolic Dysfunction in 10 to 12 Years Old Children

Abstract

BackgroundGrowing evidence shows that metabolic syndrome (MetS) is already starting in childhood however there is no consensus regarding how to diagnose this condition in pediatric population. Studies in adults show that altered levels of specific micro-RNAs are related with components of the MetS.ObjectiveWe determined the plasma levels of four MetS-associated micro-RNAs (miR-126, miR-132, mir-145 and Let-7e) in 10 to 12 years old children with or without MetS traits.DesignPediatric subjects were selected from a cohort of 3325 school-age children, and clustered by the absence (control, n = 30), or the presence of 1 (n = 50), 2 (n = 41) or 3 (n = 35) MetS traits according to Cook´s criteria. Micro-RNAs were isolated from plasma, and levels of miR-126, miR-132, miR-145 and Let-7e were determined by Taqman qPCR.ResultsRegression analysis of the different MetS traits regarding the different miRNAs analyzed showed that Let-7e presented a negative association with HDL-C levels, but a positive correlation with the number of MetS traits. Levels of miR-126 presented a positive correlation with waist circumference, waist to hip ratio, BMI, and plasma triglycerides and VLDL-C. Levels of miR-132 showed a positive correlation with waist to hip ratio. Plasma levels of Let-7e were increased (~3.4 fold) in subjects with 3 MetS traits, and showed significant AUC (0.681; 95%CI = [0.58, 0.78]; p < 0.001) in the ROC analysis which were improved when miR-126 was included in the analysis (AUC 0.729; p < 0.001). In silico analysis of the interaction of proteins derived from mRNAs targeted by Let7 and miR-126 showed an important effect of both Let-7e and miR-126 regulating the insulin signaling pathway.ConclusionsThese results suggest that changes in the plasma levels of Let-7e and miR-126 could represent early markers of metabolic dysfunction in children with MetS traits.

Let-7e sensitizes epithelial ovarian cancer to cisplatin through repressing DNA double strand break repair

“…Low serum let-7e was identified as a potential predictor for severe knee or hip osteoarthritis [43]. The plasma let-7e was found to be an early marker of metabolic syndrome in pediatric population [44]. Thus, future investigations should strive to incorporate let-7e detection, both in EOC tissue and in peripheral circulation, into clinical trials to evaluate whether let-7e can be used to guide decision making on usage of platinum-taxane chemotherapy and monitoring the response to chemotherapy during treatment in EOC.…”

Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA

“…It is decreased in circulation in adults with T2DM [19], and may be used to predict development of T2DM [26,27]. In children, plasma levels of miR-126 have been positively associated with BMI and plasma triacylglycerols and very-low-density lipoprotein-cholesterol (VLDL-C) [28]. Our finding of expression in HUVECs suggests a role in vascular function which is supported by studies demonstrating miR-126 to be essential for angiogenesis and vascular remodelling under shear stress [29,30] as well effects on vascular endothelial growth factor A (VEGFA) [31] abundance and the production of reactive oxygen species in HUVECs [32].…”

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence

“…A large number of miRNAs were identified as intrinsic in the pathogenesis of insulin resistance by affecting pancreatic β-cell development, insulin biosynthesis, insulin secretion, or by interacting with insulin signaling pathways [81]. In addition, several miRNAs proved to be associated with endothelial dysfunction [83], serum lipid level alterations [78, 84, 85], inflammation [86], and other additional markers of metabolic dysfunction in children [85]. Interestingly, some miRNAs are enriched in the hypothalamus, suggesting a primary role in the hypothalamic regulation of energy intake, expenditure, and body weight control [87].…”