title: MiR-486 regulates cholesterol efflux by targeting HAT1.
abstract: BACKGROUND
  Excessive cholesterol accumulation in macrophages is a major factor of foam cell formation and development of atherosclerosis. Previous studies suggested that miR-486 plays an important role in cardiovascular diseases, but the underlying mechanism is still unknown.
  
  
  OBJECTIVE
  The purpose of this study is to determine whether miR-486 regulates ATP-binding cassette transporter A1 (ABCA1) mediated cholesterol efflux, and also explore the underlying mechanism.
  
  
  RESULTS
  Based on bioinformatics analysis and luciferase reporter assay, we transfected miR-486 mimic and miR-486 inhibitor into THP-1 macrophage-derived foam cells, and found that miR-486 directly bound to histone acetyltransferase-1 (HAT1) 3'UTR, and downregulated its mRNA and protein expression. In addition, our studies through transfection with wildtype HAT1 or shHAT1 (short hairpin HAT1) revealed that HAT1 could promote the expression of ABCA1 at both mRNA and protein levels. At the same time, the acetylation levels of the lysines 5 and 12 of histone H4 were upregulated after overexpression with HAT1. Meanwhile, the results of liquid scintillation counter and high performance liquid chromatography (HPLC) showed that miR-486 promoted cholesterol accumulation in THP-1 macrophages.
  
  
  CONCLUSIONS
  These data indicated that miR-486 aggravate the cholesterol accumulation in THP-1 cells by targeting HAT1.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lan
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Cheng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Gong
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Lv
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Tan
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary T2N 4N1, Alberta, Canada.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China. Electronic address: tangchaoke@qq.com.
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; C560945:MIRN486 microRNA, human; D035683:MicroRNAs; D002784:Cholesterol; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex
keywords: ATP-binding cassette transporter A1; Atherosclerosis; Cholesterol efflux; Histone acetyltransferase 1; miR-486