title: MicroRNA-194 regulates keratinocyte proliferation and differentiation by targeting Grainyhead-like 2 in psoriasis.
abstract: MicroRNAs (miRNAs) are currently emerged as important regulators in psoriasis. Psoriasis is characterized by hyperproliferation and impaired differentiation of keratinocytes in skin lesions. miR-194 is a well-known regulator of cell proliferation and differentiation. However, the role of miR-194 in psoriasis pathogenesis remains unclear. In this study we aimed to investigate the role of miR-194 in keratinocyte hyperproliferation and differentiation. We found that miR-194 was significantly downregulated in psoriasis lesional skin. Overexpression of miR-194 inhibited the proliferation and promoted the differentiation of primary human keratinocytes, whereas miR-194 suppression promoted the proliferation and inhibited their differentiation. Bioinformatic analysis predicted that the Grainyhead-like 2 (GRHL2) was a target gene of miR-194, which we further validated with a dual-luciferase reporter assay, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blot analysis. The effect of miR-194 on cell proliferation and differentiation was significantly reversed by overexpression of GRHL2. Moreover, the expression of miR-194 and GRHL2 was inversely correlated in psoriasis lesional skin. Taken together, our results suggest that miR-194 inhibits the proliferation and promotes the differentiation of keratinocytes through targeting GRHL2. The downregulation of miR-194 expression may contribute to the pathogenesis of psoriasis and targeting miR-194 may represent a novel and potential therapeutic strategy for psoriasis.
authors.affiliation: Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu 210029, China; Department of Dermatovenereology, The Second Hospital of Nanjing, Nanjing, Jiangsu 210003, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Dermatology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Jingang
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Nanjing, Nanjing, Jiangsu 210003, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Nanjing, Nanjing, Jiangsu 210003, China.
authors.forename: Zihai
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Dermatovenereology, The Second Hospital of Nanjing, Nanjing, Jiangsu 210003, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yan
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China. Electronic address: fanweixin_njmu@163.com.
authors.forename: Weixin
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu 210029, China. Electronic address: chuansu_njmu@163.com.
authors.forename: Chuan
authors.initials: C
authors.lastname: Su
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C470830:GRHL2 protein, human; C554846:MIRN194 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors
keywords: GRHL2; Keratinocyte; Psoriasis; miR-194