title: miR-29a promotes scavenger receptor A expression by targeting QKI (quaking) during monocyte-macrophage differentiation.
abstract: Monocyte differentiation into macrophages results in upregulation of miR-29a and scavenger receptor A (SRA) expression, while the expression of RNA binding protein, QKI is suppressed. Since SRA is a functionally important protein in atherosclerosis, it is imperative to understand the various mechanisms involved in its regulation specially the mechanism involving miR-29a. There are individual studies linking miR-29a to SRA or QKI to monocyte differentiation but there is no evidence of any linkage among them. Therefore, we intend to investigate the association among these three, if any, in terms of regulation of SRA expression. Hence, in this study, the differentiated macrophages were initially transfected with miR-29a or its inhibitor and it was shown that QKI is a direct target of mir-29a. In addition, it was also observed by bioinformatics analysis that 3'UTR in SRA mRNA has QKI binding site. So, we attempted to further understand the role of QKI in SRA regulation. The macrophages were manipulated either with overexpression of QKI or by its ablation and it was observed that QKI suppressed SRA at the transcriptional level. Moreover, with the help of luciferase reporter vector, it was shown that QKI inhibited SRA transcription by binding to QRE region in its 3'UTR mRNA. Furthermore, to link the QKI mediated regulation of SRA expression with its functional activity; we analyzed lipid uptake capacity of macrophages transfected with either ectopic OKI plasmid or ablated for QKI. It was observed that, indeed, QKI upregulation inhibits lipid uptake by repressing SRA expression. Overall, our study demonstrates that miR-29a inhibits QKI, which in turn results in upregulation of SRA and lipid uptake.
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zan
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Zewei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China. Electronic address: zjh_john@medmail.com.cn.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D050356:Lipid Metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D061251:Primary Cell Culture; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C490832:QKI protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D051117:Scavenger Receptors, Class A; D008156:Luciferases
keywords: Differentiation; QKI; SRA; miR-29a and lipid uptake