MicroRNA-370 controls the expression of MicroRNA-122 and Cpt1α and affects lipid metabolism[S]

Journal of Lipid Research

Ira J. Goldberg¹  Yaeko Hiyama²  Konstantinos Drosatos³  Dimitrios Iliopoulos⁴  Vassilis I. Zannis⁵ 

[1] Division of Preventive Medicine and Nutrition, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY;Molecular Genetics, Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA;Department of Basic Sciences, University of Crete Medical School, Heraklion, Greece;Department of Biological Chemistry and Molecular Pharmacology, School of Medicine, Harvard University, Boston, MA;Division of Preventive Medicine and Nutrition, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY;

关键词: microRNA-122;    microRNA-370;    carnitine palmitoyl transferase-1a;    triglyceride biosynthesis;    fatty acid biosynthesis;    β oxidation;   

DOI  :  

来源: DOAJ

【 摘 要 】

We previously observed that treatment of mice with a dominant negative form of cJun (dn-cJun) increased the expression of genes involved in lipid metabolism and modulated the expression of nine microRNAs (miR). To investigate the potential effect of these miRs on the expression of the genes of lipid metabolism, we performed studies in cultured HepG2 cells. Transfection of HepG2 cells with sense or antisense miR-370 or miR-122 upregulated and downregulated, respectively, the transcription factor sterol-regulatory element binding protein 1c (SREBP-1c) and the enzymes diacylglycerol acyltransferase-2 (DGAT2), fatty acid synthase (FAS), and acyl-CoA carboxylase 1 (ACC1) that regulate fatty acid and triglyceride biosynthesis. The other seven miRs identified by the miR array screening did not affect the expression of lipogenic genes. miR-370 upregulated the expression of miR-122. Furthermore, the effect of miR-370 on the expression of the lipogenic genes was abolished by antisense miR-122. miR-370 targets the 3′ untranslated region (UTR) of Cpt1α, and it downregulated the expression of the carnitine palmitoyl transferase 1α (Cpt1α) gene as well as the rate of β oxidation. Our data suggest that miR-370 acting via miR-122 may have a causative role in the accumulation of hepatic triglycerides by modulating initially the expression of SREBP-1c, DGAT2, and Cpt1α and, subsequently, the expression of other genes that affect lipid metabolism.

【 授权许可】

Unknown