Shaw Tyler A, Singaravelu Ragunath, Powdrill Megan H, Nhan Jordan, Ahmed Nadine, Özcelik Dennis, Pezacki John Paul
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada.
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
iScience. 2018 Dec 21;10:149-157. doi: 10.1016/j.isci.2018.11.028. Epub 2018 Nov 20.
MicroRNAs (miRNAs) are part of a complex regulatory network that modulates cellular lipid metabolism. Here, we identify miR-124 as a regulator of triglyceride (TG) metabolism. This study advances our knowledge of the role of miR-124 in human hepatoma cells. Transcriptional profiling of Huh7.5 cells overexpressing miR-124 reveals enrichment for host factors involved in fatty acid oxidation among repressed miRNA targets. In addition, miR-124 down-regulates arylacetamide deacetylase (AADAC) and adipose triglyceride lipase, lipases proposed to mediate breakdown of hepatic TG stores for lipoprotein assembly and mitochondrial β-oxidation. Consistent with the inhibition of TG and fatty acid catabolism, miR-124 expression promotes cellular TG accumulation. Interestingly, miR-124 inhibits the production of hepatitis C virus, a virus that hijacks lipid pathways during its life cycle. Antiviral activity of miR-124 is consistent with repression of AADAC, a pro-viral host factor. Overall, our data highlight miR-124 as a novel regulator of TG metabolism in human hepatoma cells.
微小RNA（miRNA）是调节细胞脂质代谢的复杂调控网络的一部分。在此，我们确定miR-124是甘油三酯（TG）代谢的调节因子。这项研究推进了我们对miR-124在人肝癌细胞中作用的认识。对过表达miR-124的Huh7.5细胞进行转录谱分析，结果显示在受抑制的miRNA靶标中，参与脂肪酸氧化的宿主因子富集。此外，miR-124下调芳基乙酰胺脱乙酰酶（AADAC）和脂肪甘油三酯脂肪酶，这些脂肪酶被认为介导肝脏TG储存的分解以用于脂蛋白组装和线粒体β氧化。与TG和脂肪酸分解代谢的抑制一致，miR-124的表达促进细胞TG积累。有趣的是，miR-124抑制丙型肝炎病毒的产生，丙型肝炎病毒在其生命周期中劫持脂质途径。miR-124的抗病毒活性与对前病毒宿主因子AADAC的抑制一致。总体而言，我们的数据突出了miR-124作为人肝癌细胞中TG代谢的新型调节因子。
