title: miR-613 regulates cholesterol efflux by targeting LXRα and ABCA1 in PPARγ activated THP-1 macrophages.
abstract: Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Although PPARγ is known to be a potent sterol sensor that play a fundamental role in cholesterol metabolism, the potential effects of PPARγ responsive miRNA still need to be revealed. In this study, we found that miR-613 is inversely correlated with LXRα and ABCA1 in PPARγ activated THP-1 cells. PPARγ negatively regulates the expression of miR-613 at transcriptional level, and miR-613 suppressed LXRα and ABCA1 by targeting the 3'-UTR of their mRNAs. Furthermore, downregulation of LXRα and ABCA1 by miR-613 inhibited cholesterol efflux from PPARγ activated THP-1 macrophages. These results revealed an alternative mechanism for PPARγ regulation and provided a potential target for the treatment of cholesterol metabolic diseases.
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ranzun
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: heguoxiang.tmmu@gmail.com.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions; D064286:ATP Binding Cassette Transporter 1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001693:Biological Transport, Active; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D000071518:Liver X Receptors; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020413:3' Untranslated Regions; C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000071518:Liver X Receptors; C561374:MIRN613 microRNA, human; D035683:MicroRNAs; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D012333:RNA, Messenger; D002784:Cholesterol
keywords: ABCA1; Cholesterol efflux; LXRα; MicroRNA-613; PPARγ