Center of Excellence in Translational Medicine, CEMT-BIOREN & Department of Basic Sciences, Universidad de La Frontera, Av. Alemania 0458, Temuco 4810296, Chile.
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes 580, Sao Paulo 05508-000, Brazil.
Int J Mol Sci. 2021 Feb 2;22(3):1468. 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 ( < 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta-, KRAS proto-oncogene, GTPase- and suppressor of cytokine signaling 1-) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and mRNA levels were increased in MetS patients ( < 0.05), and these effects were correlated with the number of MetS diagnostic criteria ( < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high expression, and serum hsCRP ( < 0.05). miR-155 was negatively correlated with , HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin ( < 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
本研究探讨了与肥胖患者代谢综合征(MetS)和心脏代谢风险相关的循环 miRNA 和靶基因。使用小 RNA 测序评估了 12 名肥胖患者(6 名 MetS 和 6 名非 MetS)的外周血 mirN 组。在更大的肥胖患者样本(48 名 MetS 和 32 名非 MetS)中,通过 qPCR 进一步分析了差异表达的 miRNA 和靶基因。使用计算机工具研究了 miRNA:mRNA 相互作用。miRNome 分析确定了 MetS 患者与非 MetS 患者相比有 10 个下调的 miRNA(<0.05)。计算机研究显示,三个 miRNA(miR-155、miR-181a 和 let-7a)及其预测靶基因(CCAAT/增强子结合蛋白β、KRAS 原癌基因、GTP 酶和细胞因子信号转导抑制物 1-)可能在胰岛素受体信号通路中发挥作用。MetS 患者的 miR-155 表达降低, 表达增加(<0.05),这些效应与 MetS 诊断标准的数量相关(<0.05)。HOMA-IR(>7.6)增加与低 miR-155 水平、高 表达和血清 hsCRP 相关(<0.05)。miR-155 与 、HOMA-IR 和血浆纤维蛋白原呈负相关,与血清脂联素呈正相关(<0.05)。循环 miR-155 的下调与胰岛素抵抗、血糖控制不佳和增加的 MetS 相关心脏代谢风险相关,这些效应可能通过与