MicroRNA-98 regulates hepatic cholesterol metabolism via targeting sterol regulatory element-binding protein 2
- Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250021 (China)
- The Second Department of Surgery, Hospital of Traditional Chinese Medicine, Lingcheng, Dezhou, Shandong Province, 253500 (China)
- Department of General Surgery, Dongchangfu People's Hospital, Liaocheng, Shandong Province, 252000 (China)
- The First Department of General Surgery, Pingyuan People's Hospital, Pingyuan, Dezhou, Shandong Province, 253100 (China)
- The Second Department of General Surgery, Pingyuan People's Hospital, Pingyuan, Dezhou, Shandong Province, 253100 (China)
- Department of General Surgery, Laoling People's Hospital, Laoling, Dezhou, Shandong Province, 253600 (China)
- Department of General Surgery, Yucheng People's Hospital, Yucheng, Dezhou, Shandong Province, 251200 (China)
- School of Medicine, Shandong University, Jinan, Shandong Province, 250012 (China)
Highlights: • The expression of miR-98 decreased while the expression of SREBP-2 increased in hypercholesterolemic patients. • SREBP-2 is a direct target gene of miR-98. • The effect of miR-98 on cholesterol metabolism is mediated by SREBP-2. • Overexpression of miR-98 reduced cholesterol level in vitro and in vivo. Hypercholesterolemia is an important risk factor for coronary heart disease. Although a lot of research has been conducted, the regulation of cholesterol metabolism is still largely unknown. Some miRNAs have been found to play critical role in the cholesterol metabolism. MiR-98 is a miRNA whose function has been reported mainly in tumorigenesis. In this study, we elucidate a novel role of miR-98 in cholesterol metabolism. We found that the expression of miR-98 was decreased significantly in hypercholesterolemic patients compared with healthy control subjects. Furthermore, we identified that SREBP-2, an important transcriptional factor in cholesterol metabolism, was a direct target of miR-98. Overexpression of miR-98 significantly repressed the 3′-UTR reporter activities of SREBP-2 in a dose-dependent manner in HepG2 cells, while the effect of miR-98 was blocked when the binding site of miR-98 within the SREBP-2 3′-UTR was mutated. And overexpression of miR-98 reduced both the mRNA and protein levels of HMGCR and LDLR significantly in vitro, which are two target genes of SREBP-2. Furthermore, MiR-98 overexpression reduced the intracellular total cholesterol levels dramatically. Moreover, we overexpressed the miR-98 by lentiviral tail vein injection in vivo. Compared with the control mice, the miR-98 overexpression mice showed lower serum cholesterol level and decreased SREBP-2, HMGCR as well as LDLR expression. Our data confirmed that reduced expression of miR-98 potentially contributes to disturbance of cholesterol metabolism. MiR-98 might be a novel therapeutic target to hypercholesterolemia.
- OSTI ID:
- 23103523
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 504, Issue 2; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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