Identification of novel circulating miRNAs biomarkers for healthy obese and lean children

Abstract

Abstract Background The prevalence of childhood obesity and overweight has risen globally, leading to increased rates of metabolic disorders. Various factors, including genetic, epigenetic, and environmental influences such as diet and physical activity, contribute to pediatric obesity. This study aimed to identify specific circulating miRNAs as potential biomarkers for assessing obesity in children. Methods Thirty children, including 15 obese and 15 extremely thin individuals, were selected for this study. MiRNA expression in circulating plasma was assessed using miRNA microarrays. The reliability of differential miRNA expression was confirmed using TaqMan qPCR. The correlation between miRNAs and obesity was analyzed through multiple linear regression, receiver operator characteristic (ROC) curve analysis, and odds ratio (OR) calculations. Bioinformatics tools were utilized to identify target genes for the selected miRNAs, and a functional network map was constructed. Results A total of 36 differentially expressed miRNAs were identified through gene chip analysis, and TaqMan qPCR validation confirmed the upregulation of seven miRNAs: hsa-miR-126-3p, hsa-miR-15b-5p, hsa-miR-199a-3p, hsa-miR-20a-5p, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-24-3p. Among these, hsa-miR-15b-5p and hsa-miR-223-3p exhibited a statistically significant difference except for hsa-miR-23a-3p. These two miRNAs showed more predicted target genes related to obesity than others. Multiple linear regression analysis revealed an association between obesity and hsa-miR-15b-5p and hsa-miR-223-3p [10.529 (4.974–16.084), -10.225 (-17.852~ -2.657)]. Even after adjusting for age and sex, these two miRNAs remained associated with obesity [8.936 (3.572–14.301), -8.449(-15.634~ -1.303)]. The area under the ROC curve (AUC) reached values of 0.816, 0.711, and 0.929, respectively. Odds ratio analysis demonstrated a significant correlation between obesity and hsa-miR-15b-5p (OR = 143, 95% CI 5.80 to 56,313, p = 0.024) and between obesity and hsa-miR-223-3p (OR = 0.01, 95% CI 0.00 to 0.23, p = 0.037). Importantly, hsa-miR-15b-5p was found to have numerous target genes associated with the FoxO, insulin, Ras, and AMPK signaling pathways. Conclusions Differential miRNA expression profiles in the circulation of obese children compared to controls suggest underlying metabolic abnormalities. Hsa-miR-15b-5p and hsa-miR-223-3p may be considered as molecular markers for the screening of obese children and populations at risk of developing metabolic syndrome.

Keywords

• Child
• Simple obesity
• microRNA
• Target gene