MicroRNA-27a/b regulates cellular cholesterol efflux, influx and esterification/hydrolysis in THP-1 macrophages
Authors: Wu-Jun Chen
Jian-Feng Wu
Yun-Cheng Lv
Xiang-Yu Liu
Chao-Ke Tang
Min Zhang
Juan Peng
Da-Wei Zhang
Kong Chen
Shi-Lin Tang
Jia-Lin Wang
Yan-Yan Tang
Deng-Pei Tang
Feng Yao
Zhong-Cheng Mo
Ping-Ping He
Xin-Ping Ouyang
Guo-Ping Tian
Xi-Long Zheng
Francisco S Cayabyab
Yuan Li
Journal: Atherosclerosis (2014)
Discipline: CLINICAL MEDICINE
Keywords: ABCA1; ACAT1; Atherosclerosis; CD36; Cholesterol homeostasis
Affiliations: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China., 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., Department of Intensive Care Unit, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China., Department of Histology and Embryology, University of South China, Hengyang 421001, China., Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan S7H 5E5, Canada., Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan S7H 5E5, Canada., Department of Pediatrics and Group on The Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada., 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., Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China. Electronic address: ., 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: .

Abstract:  Rationale: 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. Methods and 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. Conclusion: 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. 

Retracted: No

PubPeer comments:
 Figures 3 and 5. This paper is part of a growing number of papers by the same senior author on topics related to lipid metabolism and atherosclerosis that contain questionable data and images. ![file] , 
 Copy pasted from https: doi.org 10.1016 j.atherosclerosis.2021.06.919 :  Editorial expression of concern: u201cMicroRNA-27a b regulates cellular cholesterol efflux, influx and esterification hydrolysis in THP-1 macrophagesu201d [Atherosclerosis Volume 234, Issue 1, May 2014, Pages 54-64]. Published:June 25, 2021. The Editors of Atherosclerosis are issuing an expression of concern to alert readers that credible concerns have been raised regarding the quality of some data in the article above. See also https: retractionwatch.com 2021 07 09 they-seem-to-mean-business-cardiology-journal-flags-papers-cited-hundreds-of-times ,