Dietary lipids modulate the expression of miR‐107, a miRNA that regulates the circadian system

Abstract

Scope: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 (PUFAs) 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. Results: Among the modulated miRNAs, miR-107 was differentially expressed by all treatments and this modulation was independent of its hosting gene, panthothenate kinase 1, 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 circadian locomotor output cycles kaput gene results in the deregulation of the circadian rhythm of the cells. Conclusion: Since chronodisruption has been linked to metabolic disorders such as type 2 diabetes, atherosclerosis, obesity, and CVD, our findings suggest that miR-107 could represent a new approach for pharmacological treatment of these diseases.

microRNA‐107 protects against inflammation and endoplasmic reticulum stress of vascular endothelial cells via KRT1‐dependent Notch signaling pathway in a mouse model of coronary atherosclerosis

“…Overexpression of miR‐93 has been reported to be useful in treating coronary atherosclerosis (He et al, ). More important, a previous study had revealed that miR‐107 was expected to be a novel therapeutic direction for various diseases including atherosclerosis (Daimiel‐Ruiz et al, ). On the basis of those findings, our results verified the hypothesis that miR‐107 may be an antiatherosclerosis miRNA as well.…”

MicroRNAs at the epicenter of intestinal homeostasis

“…Indeed, metabolism of dietary lipids by gut microbiota results in production of energy as well as signaling molecules that influence multiple pathways . Just recently it was shown that in vitro treatment of Caco‐2 cells with dietary lipids such as cholesterol, docosahexanoic acid, and conjugated linoleic acid resulted in 29 differentially regulated miRNAs . Among these, miR‐107, previously implicated in the regulation of metabolic diseases and cancer , was significantly up‐regulated by all these three lipids.…”

“…Among these, miR‐107, previously implicated in the regulation of metabolic diseases and cancer , was significantly up‐regulated by all these three lipids. Although the molecular mechanism through which miRNA‐107 impacts metabolic pathways is not fully understood, it was suggested that this could be through modulation of the circadian system . It was also reported that gut microbiota down‐regulates miRNA‐107 in myeloid cells and in macrophages .…”

Circadian processes in the RNA life cycle

“…In particular, cell‐based studies have implicated miR‐192, miR‐194 and miR‐29 in the regulation of the human Per gene family (Nagel, Clijsters, & Agami, ) and miR‐24, miR‐29a and miR‐30a in the regulation of the mouse Per gene family (Chen, D'Alessandro, & Lee, ; Zhao et al, ) (see Figure ). In humans, miR‐107 controls the circadian rhythm of cells by binding to the Clock gene (Daimiel‐Ruiz et al, ). In mice, miR‐494, miR‐142‐3p and miR‐27b‐3p may function as post‐transcriptional modulators of Bmal1 , but only miR‐494 follows a circadian expression pattern (Shende, Goldrick, Ramani, & Earnest, ; Zhang et al, ).…”