title: Long noncoding RNA LINC00305 promotes inflammation by activating the AHRR-NF-κB pathway in human monocytes.
abstract: Accumulating data from genome-wide association studies (GWAS) have provided a collection of novel candidate genes associated with complex diseases, such as atherosclerosis. We identified an atherosclerosis-associated single-nucleotide polymorphism (SNP) located in the intron of the long noncoding RNA (lncRNA) LINC00305 by searching the GWAS database. Although the function of LINC00305 is unknown, we found that LINC00305 expression is enriched in atherosclerotic plaques and monocytes. Overexpression of LINC00305 promoted the expression of inflammation-associated genes in THP-1 cells and reduced the expression of contractile markers in co-cultured human aortic smooth muscle cells (HASMCs). We showed that overexpression of LINC00305 activated nuclear factor-kappa beta (NF-κB) and that inhibition of NF-κB abolished LINC00305-mediated activation of cytokine expression. Mechanistically, LINC00305 interacted with lipocalin-1 interacting membrane receptor (LIMR), enhanced the interaction of LIMR and aryl-hydrocarbon receptor repressor (AHRR), and promoted protein expression as well as nuclear localization of AHRR. Moreover, LINC00305 activated NF-κB exclusively in the presence of LIMR and AHRR. In light of these findings, we propose that LINC00305 promotes monocyte inflammation by facilitating LIMR and AHRR cooperation and the AHRR activation, which eventually activates NF-κB, thereby inducing HASMC phenotype switching.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Wen-Tian
authors.initials: WT
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Shen-Shen
authors.initials: SS
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry, The University of Hong Kong, Hong Kong SAR, P. R. China.|Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P. R. China.
authors.forename: Mulin Jun
authors.initials: MJ
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Zhu-Qin
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: De-Long
authors.initials: DL
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Vascular Surgery, Beijing Hospital, Beijing 100005, P. R. China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Biochemistry, The University of Hong Kong, Hong Kong SAR, P. R. China.|Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P. R. China.|Center for Individualized Medicine, Mayo Clinic Arizona &Department of Biomedical Informatics, Arizona State University, Scottsdale, AZ, 85259, USA.
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Hou-Zao
authors.initials: HZ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.|Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100005, P. R. China.
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
mesh_terms: D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D021381:Protein Transport; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016328:NF-kappa B; D062085:RNA, Long Noncoding; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; C492162:AHRR protein, human; C430233:LMBR1L protein, human