Journal article
Identification of miR-185 as a regulator of de novo cholesterol biosynthesis and low density lipoprotein uptake
Journal of lipid research, v 55(2), pp 226-238
01 Feb 2014
PMID: 24296663
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Dysregulation of cholesterol homeostasis is associated with various metabolic diseases, including atherosclerosis and type 2 diabetes. The sterol response element binding protein (SREBP)-2 transcription factor induces the expression of genes involved in de novo cholesterol biosynthesis and low density lipoprotein (LDL) uptake, thus it plays a crucial role in maintaining cholesterol homeostasis. Here, we found that overexpressing microRNA (miR)-185 in HepG2 cells repressed SREBP-2 expression and protein level. miR-185-directed inhibition caused decreased SREBP-2-dependent gene expression, LDL uptake, and HMG-CoA reductase activity. In addition, we found that miR-185 expression was tightly regulated by SREBP-1c, through its binding to a single sterol response element in the miR-185 promoter. Moreover, we found that miR-185 expression levels were elevated in mice fed a high-fat diet, and this increase correlated with an increase in total cholesterol level and a decrease in SREBP-2 expression and protein. Finally, we found that individuals with high cholesterol had a 5-fold increase in serum miR-185 expression compared with control individuals. Thus, miR-185 controls cholesterol homeostasis through regulating SREBP-2 expression and activity. In turn, SREBP-1c regulates miR-185 expression through a complex cholesterol-responsive feedback loop. Thus, a novel axis regulating cholesterol homeostasis exists that exploits miR-185-dependent regulation of SREBP-2 and requires SREBP-1c for function.
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Details
- Title
- Identification of miR-185 as a regulator of de novo cholesterol biosynthesis and low density lipoprotein uptake
- Creators
- Muhua Yang - AnsysWeidong Liu - AnsysChristina Pellicane - AnsysChristine Sahyoun - AnsysBiny K. Joseph - AnsysChristina Gallo-Ebert - AnsysMelissa Donigan - AnsysDevanshi Pandya - AnsysCaroline Giordano - AnsysAdam Bata - AnsysJoseph T. Nickels - Ansys
- Publication Details
- Journal of lipid research, v 55(2), pp 226-238
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- Genesis Biotechnology Group
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000330535800007
- Scopus ID
- 2-s2.0-84893357948
- Other Identifier
- 991021229886104721
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- Web of Science research areas
- Biochemistry & Molecular Biology