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This study explored circulating miRNAs and target genes associated with metabolic syndrome (MetS) and cardiometabolic risk in obese patients. Small-RNA sequencing was used to assess the peripheral blood miRNome of 12 obese subjects (6 MetS and 6 non-MetS). Differentially expressed miRNAs and target genes were further analyzed by qPCR in a larger sample of obese patients (48 MetS and 32 non-MetS). miRNA:mRNA interactions were studied using in silico tools. miRNome analysis identified 10 downregulated miRNAs in MetS compared to non-Met patients ( p &lt; 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta- CEBPB , KRAS proto-oncogene, GTPase- KRAS and suppressor of cytokine signaling 1- SOCS1 ) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and CEBPB mRNA levels were increased in MetS patients ( p &lt; 0.05), and these effects were correlated with the number of MetS diagnostic criteria ( p &lt; 0.05). Increased HOMA-IR (&gt;7.6) was associated with low miR-155 levels, high CEBPB expression, and serum hsCRP ( p &lt; 0.05). miR-155 was negatively correlated with CEBPB , HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin ( p &lt; 0.05). Downregulation of circulating miR-155 is associated with insulin resistance, poor glycemic control, and increased MetS-related cardiometabolic risk, and these effects are potentially mediated by interaction with CEBPB.

Peripheral Blood miRome Identified miR-155 as Potential Biomarker of MetS and Cardiometabolic Risk in Obese Patients