title: NF-κB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis.
abstract: NF-κB is constitutively activated in psoriatic epidermis. However, how activated NF-κB promotes keratinocyte hyperproliferation in psoriasis is largely unknown. Here we report that the NF-κB activation triggered by inflammatory cytokines induces the transcription of microRNA (miRNA) miR-31, one of the most dynamic miRNAs identified in the skin of psoriatic patients and mouse models. The genetic deficiency of miR-31 in keratinocytes inhibits their hyperproliferation, decreases acanthosis and reduces the disease severity in psoriasis mouse models. Furthermore, protein phosphatase 6 (ppp6c), a negative regulator that restricts the G1 to S phase progression, is diminished in human psoriatic epidermis and is directly targeted by miR-31. The inhibition of ppp6c is functionally important for miR-31-mediated biological effects. Moreover, NF-κB activation inhibits ppp6c expression directly through the induction of miR-31, and enhances keratinocyte proliferation. Thus, our data identify NF-κB-induced miR-31 and its target, ppp6c, as critical factors for the hyperproliferation of epidermis in psoriasis.
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Yan
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Zhenyao
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Fangzhou
authors.initials: F
authors.lastname: Lou
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ke
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Su
authors.affiliation: Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Jianxiu
authors.initials: J
authors.lastname: Yu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Microbiology &Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Yu
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chin
authors.affiliation: 1] Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China [2] Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000276:immunology; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D016207:Cytokines; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; C539917:Mirn31 microRNA, mouse; D016328:NF-kappa B; D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases; C106079:protein phosphatase 6