title: MicroRNA-27a/b regulates cellular cholesterol efflux, influx and esterification/hydrolysis in THP-1 macrophages.
abstract: BACKGROUND
  Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis.
  
  
  OBJECTIVE
  We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis.
  
  
  RESULTS
  In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3' UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages.
  
  
  CONCLUSIONS
  These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China; Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Wu-Jun
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Intensive Care Unit, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China.
authors.forename: Shi-Lin
authors.initials: SL
authors.lastname: Tang
authors.affiliation: Department of Histology and Embryology, University of South China, Hengyang 421001, China.
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Mo
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Tang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Kong
authors.initials: K
authors.lastname: Chen
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: He
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Lv
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Ouyang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan S7H 5E5, Canada.
authors.forename: Deng-Pei
authors.initials: DP
authors.lastname: Tang
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan S7H 5E5, Canada.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Cayabyab
authors.affiliation: Department of Pediatrics and Group on The Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.affiliation: Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China. Electronic address: tianguopingnhfe@163.com.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Tian
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China. Electronic address: tangchaoke@qq.com.
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004951:Esterification; D006801:Humans; D006868:Hydrolysis; D008264:Macrophages / Q000378:metabolism*; D035683:MicroRNAs / Q000502:physiology*
chemical_list: C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D002784:Cholesterol
keywords: ABCA1; ACAT1; Atherosclerosis; CD36; Cholesterol homeostasis; LPL; apoA1; miR-27a/b