Daimiel-Ruiz Lidia, Klett-Mingo Mercedes, Konstantinidou Valentini, Micó Victor, Aranda Juan F, García Belén, Martínez-Botas Javier, Dávalos Alberto, Fernández-Hernando Carlos, Ordovás Jose M
Nutritional Genomics of Cardiovascular Disease and Obesity, IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain.
Mol Nutr Food Res. 2015 Mar;59(3):552-65. doi: 10.1002/mnfr.201400616. Epub 2015 Jan 21.
The increased prevalence of cardiovascular diseases (CVDs) has been hypothesized to be the result of an increased exposure to a host of atherogenic environmental factors, paramount among them being unhealthy dietary habits. Long-chain n-3 polyunsaturated fatty acids have been shown to have cardio protective effects, partially due to their ability to regulate gene expression. In this regard, increasing attention has been devoted to the role of miRNAs as regulators of multiple metabolic pathways whose deregulation has been associated with CVD risk.
In this work, we investigated whether miRNA expression was regulated by docosahexanoic acid, conjugated linoleic acid, and cholesterol in Caco-2 cells. The modulated miRNAs, miR-107 was differentially expressed by all treatments and this modulation was independent of its hosting gene, PANK1, possibly through its own promoter, which contains binding sites for metabolically relevant transcription factors. Among the putative target genes of miR-107, we found some genes with key roles in circadian rhythm. Specifically, we demonstrated that binding of miR-107 to the CLOCK gene results in the deregulation of the circadian rhythm of the cells.
Since chronodisruption has been linked to metabolic disorders such as type 2 diabetes, atherosclerosis, obesity, and CVD, our findings suggests that miR-107 could represent a new approach for pharmacological treatment of these diseases.
心血管疾病（CVDs）患病率的增加被认为是由于接触了一系列致动脉粥样硬化环境因素增加所致，其中最重要的是不健康的饮食习惯。长链n-3多不饱和脂肪酸已被证明具有心脏保护作用，部分原因是它们能够调节基因表达。在这方面，人们越来越关注微小RNA（miRNAs）作为多种代谢途径调节因子的作用，这些代谢途径的失调与心血管疾病风险相关。
在这项研究中，我们研究了二十二碳六烯酸、共轭亚油酸和胆固醇是否在Caco-2细胞中调节miRNA表达。受调控的miRNA，即miR-107在所有处理中均有差异表达，且这种调节与其宿主基因PANK1无关，可能是通过其自身的启动子，该启动子包含与代谢相关转录因子的结合位点。在miR-107的假定靶基因中，我们发现了一些在昼夜节律中起关键作用的基因。具体而言，我们证明了miR-107与生物钟基因（CLOCK）的结合导致细胞昼夜节律失调。
由于昼夜节律紊乱与2型糖尿病、动脉粥样硬化、肥胖和心血管疾病等代谢紊乱有关，我们的研究结果表明，miR-107可能代表了一种治疗这些疾病的新的药理学方法。
