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

• Published in: International journal of molecular sciences Vol. 22; no. 3; p. 1468
• Main Authors: Cerda, Alvaro, Amaral, Adonai Aralim, de Oliveira, Raquel, Moraes, Tamiris Invencioni, Braga, Aécio Assunção, Graciano-Saldarriaga, Magda Elizabeth, Fajardo, Cristina Moreno, Hirata, Thiago Dominguez Crespo, Bonezi, Vivian, Campos-Salazar, Antony Brayan, Dorea, Egidio Lima, Bernik, Marcia Martins Silveira, Hirata, Mario Hiroyuki, Hirata, Rosario Dominguez Crespo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.02.2021; MDPI
• Subjects: Adiponectin - blood; Adult; Biomarkers; Biomarkers - blood; Body mass index; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - etiology; Cardiovascular Diseases - metabolism; CCAAT-Enhancer-Binding Protein-beta - blood; CCAAT-Enhancer-Binding Protein-beta - metabolism; Cholesterol; Computer Simulation; Cytokines; Diabetes; DNA methylation; Epigenetics; Female; Fibrinogen - analysis; Gene expression; Hemoglobin; Humans; Hypertension; Insulin resistance; Laboratories; Male; Metabolic Syndrome - blood; Metabolic Syndrome - epidemiology; Metabolic Syndrome - etiology; Metabolic Syndrome - metabolism; Metabolism; MicroRNAs; MicroRNAs - blood; MicroRNAs - metabolism; Middle Aged; Obesity; Obesity - complications; Obesity - metabolism; Receptor, Insulin - metabolism; Risk Factors; Sequence Analysis, RNA; Signal Transduction; Validation studies; United States > US; metabolic syndrome; microRNAs; CEBPB; cardiometabolic risk; miR-155; obesity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22031468

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.