Human MicroRNA-548p Decreases Hepatic Apolipoprotein B Secretion and Lipid Synthesis.

Liye Zhou, M Mahmood Hussain

Arteriosclerosis, thrombosis, and vascular biology 2017 May

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MicroRNAs (miRs) play important regulatory roles in lipid metabolism. Apolipoprotein B (ApoB), as the only essential scaffolding protein in the assembly of very-low-density lipoproteins, is a target to treat hyperlipidemia and atherosclerosis. We aimed to find out miRs that reduce apoB expression. Bioinformatic analyses predicted that hsa-miR-548p can interact with apoB mRNA. MiR-548p or control miR was transfected in human and mouse liver cells to test its role in regulating apoB secretion and mRNA expression levels. Site-directed mutagenesis was used to identify the interacting site of miR-548p in human apoB 3'-untranslated region. Fatty acid oxidation and lipid syntheses were examined in miR-548p overexpressing cells to investigate its function in lipid metabolism. We observed that miR-548p significantly reduces apoB secretion from human hepatoma cell s and primary hepatocytes. Mechanistic studies showed that miR-548p interacts with the 3'-untranslated region of human apoB mRNA to enhance post-transcriptional degradation. Bioinformatic algorithms suggested 2 potential binding sites of miR-548p on human apoB mRNA. Site-directed mutagenesis studies revealed that miR-548p targets site I involving both seed and supplementary sequences. MiR-548p had no effect on fatty acid oxidation but significantly decreased lipid synthesis in human hepatoma cell s by reducing HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and ACSL4 (Acyl-CoA synthetase long-chain family member 4) enzymes involved in cholesterol and fatty acid synthesis. In summary, miR-548p reduces lipoprotein production and lipid synthesis by reducing expression of different genes in human liver cell s. These studies suggest that miR-548p regulates apoB secretion by targeting mRNA. It is likely that it could be useful in treating atherosclerosis, hyperlipidemia, and hepatosteatosis. © 2017 American Heart Association, Inc.

Citation

Liye Zhou, M Mahmood Hussain. Human MicroRNA-548p Decreases Hepatic Apolipoprotein B Secretion and Lipid Synthesis. Arteriosclerosis, thrombosis, and vascular biology. 2017 May;37(5):786-793