title: Upregulation of miRNA-155 expression by OxLDL in dendritic cells involves JAK1/2 kinase and transcription factors YY1 and MYB.
abstract: Dendritic cells (DCs) have been implicated in the pathogenesis of atherosclerosis (AS). Whereas the pathogenic role of oxidized low-density lipoprotein (oxLDL) in the development and progression of AS has been recognized previously, the contribution of microRNA-155 (miR-155) to AS was previously not fully understood. It had also been noted that miR-155 levels were upregulated by oxLDL in various cell types under different (patho)physiological conditions, but its underlying mechanisms had not been examiend in detail. Thus, in the present study, we observed that oxLDL treatment increased miR-155 expression in DCs, and transfecting DCs with siRNA against scavenger receptor A (SRA) revealed that repression of SRA attenuated this upregulation. We also noted that miR-155 negatively regulated SRA expression by suppressing the JNK pathway. Furthermore, we noted that Yin Yang 1 (YY1) and V-Myb avian myeloblastosis viral oncogene homolog (MYB), which were also upregulated by oxLDL, directly bound to the cognate sequences of the promoter region of miR-155 to activate its transcription. In addition, using SP600125, a specific inhibitor for c-Jun N-terminal kinase (JNK) signaling, we demonstrated that JNK signaling was involved in the miR‑155-mediated suppression of SRA expression. Thus, in the present study we uncovered the molecular mechanism through which miR-155 expression is regulated by oxLDL, and we also identified a negative feedback loop, miR‑155-JNK-SRA-miR-155. Our findings thus provide novel insights into the regulatory network underlying the expression and activity of miR-155 in DCs.
authors.affiliation: Department of Cardiology, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Cardiology, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Zewei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Cardiology, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
mesh_terms: D018955:CD36 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation; D050986:YY1 Transcription Factor / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D020598:Proto-Oncogene Proteins c-myb; D050986:YY1 Transcription Factor; C099252:oxidized low density lipoprotein; D053613:Janus Kinase 1; D053614:Janus Kinase 2