The LINC01176-miR-218-5p-IL-36G Network is Responsible for the Pathogenesis of Psoriasis by Promoting Inflammation

Abstract

Zongfeng Zhao,1,* Jie Cheng,2,* Wanqun Sun,1 Jian Zhu,3 Sheng Lu,3 Yanyan Feng,4 Zhendong Song,5 Yali Yang,6 Xiujuan Wu3 1Department of Scientific Research, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 4Chengdu Second People’s Hospital, Chengdu, Sichuan Province, People’s Republic of China; 5WLSA Shanghai Academy, Shanghai, People’s Republic of China; 6Department of Dermatology, Shanghai Ninth Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yali Yang, Department of Dermatology, Shanghai Ninth Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, No. 639, Manufacturing Bureau Road, Huangpu District, Shanghai, 200011, People’s Republic of China, Email [email protected] Xiujuan Wu, Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, No. 966, Huaihai Middle Road, Xuhui District, Shanghai, 200031, People’s Republic of China, Email [email protected]: Psoriasis is an incurable chronic inflammatory skin disease. The exact function and regulatory mechanism of non-coding RNA upregulation in psoriasis remains to be elucidated. The aim of this study was to analyse the role of the lncRNA-miRNA-mRNA network of psoriasis and LINC01176 in the pathogenesis of psoriasis.Patients and Methods: We performed miRNA, lncRNA, and mRNA sequencing analysis in pretreatment and treatment psoriatic tissues and normal tissues, constructed an lncRNA-miRNA-mRNA coexpression network and screened mRNA-associated pathways using bioinformatics analysis. We further validated the regulatory role of LINC01176-miR-218-5p on the proliferation and inflammation of the psoriatic model by dual-luciferase reporter assay, cell transfection, CCK-8 method, TUNEL staining and animal model construction method. An lncRNA-miRNA-mRNA coexpression network was successfully constructed by RNA-seq data analysis.Results: We obtained the relationship between LINC01176, miR-218-5p and IL36-G. Analysis of the apoptotic and proliferative capacity of the transfected cells showed that miR-218-5p up-regulation significantly inhibited cell proliferation and promoted apoptosis. A mouse model of psoriasis was successfully established. Phenotypic observations revealed that keratin-forming cells in mice coated with LINC01176-shRNA emulsifier were significantly lower than those in the model group and close to those in the normal group. HE and immunohistochemical experiments were performed, and the results showed the role and mechanism of action of LINC01176-shRNA. Suppression of LINC01176 significantly inhibited the expression of IL-36G in psoriatic tissues. LINC01176 showed a targeting and positive correlation with IL36-G expression.Conclusion: Our study shows that LINC01176 promotes the proliferation and invasion of keratinocytes and inhibits apoptosis by targeting miR-218-5p, which acts as a repressor of the psoriasis-associated IL-36G. The shRNA-LINC01176 emulsion showed potential treatment capability in alleviating symptoms of psoriasis.Keywords: psoriasis, LINC01176, IL-36G, inflammation

Keywords

• psoriasis
• linc01176
• il-36g
• inflammation