标题:MicroRNA-98 regulates hepatic cholesterol metabolism via targeting sterol regulatory element-binding protein 2
作者:Geng, Chong; Dong, Tianyi; Jin, Weilong; Yu, Bo; Yin, Fuhui; Peng, Fengqiang; Chen, Guanmin; Ji, Chuncai; Ding, Feng
作者机构:[Geng, Chong; Dong, Tianyi] Shandong Univ, Dept Breast & Thyroid Surg, Shandong Prov Hosp, Jinan 250021, Shandong, Peoples R China.; [Jin, Weilong] 更多
通讯作者:Ding, F
通讯作者地址:[Ding, F]Shandong Univ, Sch Med, 44 Wenhuaxi Rd, Jinan 250012, Shandong, Peoples R China.
来源:BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
出版年:2018
卷:504
期:2
页码:422-426
DOI:10.1016/j.bbrc.2018.08.205
关键词:MiR-98; Cholesterol metabolism; SREBP-2; HMG-CoA reductase
摘要: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. (C) 2018 Elsevier Inc. All rights reserved.
收录类别:SCOPUS;SCIE
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052798295&doi=10.1016%2fj.bbrc.2018.08.205&partnerID=40&md5=529604638c7662f4244f4334b432742d
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