title: MicroRNAs 185, 96, and 223 repress selective high-density lipoprotein cholesterol uptake through posttranscriptional inhibition.
abstract: Hepatic scavenger receptor class B type I (SR-BI) plays an important role in selective high-density lipoprotein cholesterol (HDL-C) uptake, which is a pivotal step of reverse cholesterol transport. In this study, the potential involvement of microRNAs (miRNAs) in posttranscriptional regulation of hepatic SR-BI and selective HDL-C uptake was investigated. The level of SR-BI expression was repressed by miRNA 185 (miR-185), miR-96, and miR-223, while the uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-HDL was decreased by 31.9% (P < 0.001), 23.9% (P < 0.05), and 15.4% (P < 0.05), respectively, in HepG2 cells. The inhibition of these miRNAs by their anti-miRNAs had opposite effects in these hepatic cells. The critical effect of miR-185 was further validated by the loss of regulation in constructs with mutated miR-185 target sites. In addition, these miRNAs directly targeted the 3' untranslated region (UTR) of SR-BI with a coordinated effect. Interestingly, the decrease of miR-96 and miR-185 coincided with the increase of SR-BI in the livers of ApoE KO mice on a high-fat diet. These data suggest that miR-185, miR-96, and miR-223 may repress selective HDL-C uptake through the inhibition of SR-BI in human hepatic cells, implying a novel mode of regulation of hepatic SR-BI and an important role of miRNAs in modulating cholesterol metabolism.
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.
authors: Li
authors: L
authors: Wang
authors: Xiao-Jian
authors: XJ
authors: Jia
authors: Hua-Jun
authors: HJ
authors: Jiang
authors: Yu
authors: Y
authors: Du
authors: Fan
authors: F
authors: Yang
authors: Shu-Yi
authors: SY
authors: Si
authors: Bin
authors: B
authors: Hong
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism* / Q000502:physiology; D034622:RNA Interference; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D001057:Apolipoproteins E; D002784:Cholesterol; D008076:Cholesterol, HDL; D049410:Luciferases, Renilla; D035683:MicroRNAs; D051122:Scavenger Receptors, Class B; C552431:MIRN185 microRNA, human; C525067:MIR223, human; C541492:MIRN96 microRNA, human; C495124:SCARB1 protein, human