title: Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus.
abstract: Long noncoding RNAs (lncRNAs) have recently been identified to be tightly linked to diverse human diseases. However, our knowledge of Systemic Lupus Erythematosus (SLE)-related lncRNAs remains limited. In the present study we investigated the contribution of the lncRNA NEAT1 to the pathogenesis of SLE. Here, we found NEAT1 expression was abnormally increased in SLE patients and predominantly expressed in human monocytes. Additionally, NEAT1 expression was induced by LPS via p38 activation. Silencing NEAT1 significantly reduced the expression of a group of chemokines and cytokines, including IL-6, CXCL10, etc., which were induced by LPS continuously and in late stages. Furthermore, it was identified the involvement of NEAT1 in TLR4-mediated inflammatory process was through affecting the activation of the late MAPK signaling pathway. Importantly, there was a positive correlation between NEAT1 and clinical disease activity in SLE patients. In conclusion, the increased NEAT1 expression may be a potential contributor to the elevated production of a number of cytokines and chemokines in SLE patients. Our findings suggest lncRNA contributes to the pathogenesis of lupus and provides potentially novel target for therapeutic intervention.
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qian
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qu
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Xia
authors.affiliation: Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: La
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jianyang
authors.initials: J
authors.lastname: Ma
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.affiliation: Cellular Biomedicine Group Inc., Shanghai, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Huang
authors.affiliation: Cellular Biomedicine Group Inc., Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Cellular Biomedicine Group Inc., Shanghai, China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China; The Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: nanshensibs@gmail.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China. Electronic address: tangyuanjia028@163.com.
authors.forename: Yuanjia
authors.initials: Y
authors.lastname: Tang
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D063990:Gene Ontology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C577276:NEAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: Cytokines; Long noncoding RNA; NEAT1; Systemic lupus erythematosus; TLR4