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

• Main Authors: Alvaro Cerda, Adonai Aralim Amaral, Raquel de Oliveira, Tamiris Invencioni Moraes, Aécio Assunção Braga, Magda Elizabeth Graciano-Saldarriaga, Cristina Moreno Fajardo, Thiago Dominguez Crespo Hirata, Vivian Bonezi, Antony Brayan Campos-Salazar, Egidio Lima Dorea, Marcia Martins Silveira Bernik, Mario Hiroyuki Hirata, Rosario Dominguez Crespo Hirata
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: International Journal of Molecular Sciences
• Subjects: obesity; metabolic syndrome; microRNAs; miR-155; <i>CEBPB</i>; cardiometabolic risk
• Online Access: https://www.mdpi.com/1422-0067/22/3/1468
• ISSN: 1661-6596; 1422-0067

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 (<i>p</i> < 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta—<i>CEBPB</i>, KRAS proto-oncogene, GTPase—<i>KRAS</i> and suppressor of cytokine signaling 1—<i>SOCS1</i>) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and <i>CEBPB</i> mRNA levels were increased in MetS patients (<i>p</i> < 0.05), and these effects were correlated with the number of MetS diagnostic criteria (<i>p</i> < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high <i>CEBPB</i> expression, and serum hsCRP (<i>p</i> < 0.05). miR-155 was negatively correlated with <i>CEBPB</i>, HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin (<i>p</i> < 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 <i>CEBPB.</i>