title: Dietary lipids modulate the expression of miR-107, an miRNA that regulates the circadian system.
abstract: METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nutritional Genomics of Cardiovascular Disease and Obesity, IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Daimiel-Ruiz
authors.forename: Mercedes
authors.initials: M
authors.lastname: Klett-Mingo
authors.forename: Valentini
authors.initials: V
authors.lastname: Konstantinidou
authors.forename: Victor
authors.initials: V
authors.lastname: Micó
authors.forename: Juan F
authors.initials: JF
authors.lastname: Aranda
authors.forename: Belén
authors.initials: B
authors.lastname: García
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Botas
authors.forename: Alberto
authors.initials: A
authors.lastname: Dávalos
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Hernando
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovás
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology; D056926:CLOCK Proteins / Q000235:genetics; D018938:Caco-2 Cells / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D057906:Circadian Clocks / Q000187:drug effects / Q000235:genetics*; D059305:Diet, High-Fat; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D011345:Fenofibrate / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011401:Promoter Regions, Genetic
chemical_list: D044243:Linoleic Acids, Conjugated; C549045:MIRN107 microRNA, human; D035683:MicroRNAs; D004281:Docosahexaenoic Acids; D002784:Cholesterol; D000069059:Atorvastatin; D056926:CLOCK Proteins; C538943:CLOCK protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D011345:Fenofibrate
keywords: Circadian rhythm; DHA; Dietary lipids; miR-107