miR-467b regulates the cholesterol ester formation via targeting ACAT1 gene in RAW 264.7 macrophages.
Previous studies have shown that miR-467b plays a central role in the progression of atherosclerosis via regulating LPL expression. However, the regulatory mechanism of miR-467b in regulateing the CE and FC formation is still unclear. Interestingly, computational analysis demonstrated that ACAT1 which converts intracellular FC into the storage form of CE, and ABCA1 which promotes cellular FC efflux may be target gene of miR-467b. Here, we examined whether miR-467b could target ACAT1 and ABCA1, thereby affecting the CE and FC formation in oxLDL-treatment RAW 264.7 cells. We found that miR-467b regulates the CE:FC ratio in oxLDL-treatment RAW 264.7 macrophages, and the luciferase activity of ACAT1 is regulated by the miR-467b, but the luciferase activity of ABCA1 has no effect. Furthermore, our data suggested that miR-467b highly regulates the endogenous levels of ACAT1 expression, thereby affecting the CE formation in oxLDL-treatment RAW 264.7 macrophages. Taken together, our findings demonstrate that ACAT1 is a target gene of miR-467b, and miR-467b regulated the CE and FC formation via directly target the ACAT1 3'UTR.
Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
Bo
B
Wang
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, 28 West Changsheng Road, Hengyang 421001, Hunan, China; Nursing School, University of South China, Hengyang, Hunan 421001, China.
Ping-Ping
PP
He
Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
Gao-Feng
GF
Zeng
Departments of Urology, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China. Electronic address: 17490587@qq.com.
Tao
T
Zhang
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, 28 West Changsheng Road, Hengyang 421001, Hunan, China; Department of Physiology, The Neuroscience Institute, Medical College, University of South China, Hengyang, Hunan 421001, China. Electronic address: y1655@163.com.
Xin-Ping
XP
Ou Yang
D020413:3' Untranslated Regions / Q000235:genetics; D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D005786:Gene Expression Regulation; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020413:3' Untranslated Regions; D064286:ATP Binding Cassette Transporter 1; D000101:Acetyl-CoA C-Acetyltransferase; D002784:Cholesterol; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C577833:Abca1 protein, mouse; C569061:MIRN467 microRNA, mouse; C099252:oxidized low density lipoprotein; C506641:Acat1 protein, mouse
ABCA1; ACAT1; Atherosclerosis; CE:FC ratio; miR-467b