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- W2156765375 abstract "Genome-wide association studies (GWASs) have linked genes to various pathological traits. However, the potential contribution of regulatory noncoding RNAs, such as microRNAs (miRNAs), to a genetic predisposition to pathological conditions has remained unclear. We leveraged GWAS meta-analysis data from >188,000 individuals to identify 69 miRNAs in physical proximity to single-nucleotide polymorphisms (SNPs) associated with abnormal levels of circulating lipids. Several of these miRNAs (miR-128-1, miR-148a, miR-130b, and miR-301b) control the expression of key proteins involved in cholesterol-lipoprotein trafficking, such as the low-density lipoprotein (LDL) receptor (LDLR) and the ATP-binding cassette A1 (ABCA1) cholesterol transporter. Consistent with human liver expression data and genetic links to abnormal blood lipid levels, overexpression and antisense targeting of miR-128-1 or miR-148a in high-fat diet-fed C57BL/6J and Apoe-null mice resulted in altered hepatic expression of proteins involved in lipid trafficking and metabolism, and in modulated levels of circulating lipoprotein-cholesterol and triglycerides. Taken together, these findings support the notion that altered expression of miRNAs may contribute to abnormal blood lipid levels, predisposing individuals to human cardiometabolic disorders." @default.
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- W2156765375 date "2015-10-26" @default.
- W2156765375 modified "2023-10-02" @default.
- W2156765375 title "Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis" @default.
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- W2156765375 doi "https://doi.org/10.1038/nm.3980" @default.
- W2156765375 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4993048" @default.
- W2156765375 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26501192" @default.
- W2156765375 hasPublicationYear "2015" @default.
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