Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/ijms22031468
Keywords
obesity; metabolic syndrome; microRNAs; miR-155; CEBPB; cardiometabolic risk
Funding
- CNPq-Brazil [457334/2013-4, 462778/2014-2]
- FAPESP [2009/10069-2]
- CAPES-Brazil [001]
- Conicyt-Chile (Fondecyt) [11150445, REDI170632]
- CONICYT-Chile
- FAPESP-Brazil
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This study identified 10 downregulated miRNAs in MetS patients, with miR-155 potentially interacting with CEBPB in the insulin receptor signaling pathway. Downregulation of miR-155 was associated with insulin resistance, poor glycemic control, and increased MetS-related cardiometabolic risk, potentially mediated by interaction with CEBPB.
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 < 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 < 0.05), and these effects were correlated with the number of MetS diagnostic criteria (p < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high CEBPB expression, and serum hsCRP (p < 0.05). miR-155 was negatively correlated with CEBPB, HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin (p < 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.
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