Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 3:17:1-12.
doi: 10.2147/CCID.S444265. eCollection 2024.

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

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 Wu  3
Affiliations

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

Zongfeng Zhao et al. Clin Cosmet Investig Dermatol. .

Abstract

Purpose: 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: IL-36G; LINC01176; inflammation; psoriasis.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Analysis of the immune microenvironment of psoriatic lesions and trend gene heat map. (a) RNA-seq deconvolution showed significant activation of plasmacytoid dendritic memory cells and T cell CD4+ Th1 in the model group, with the treated group returning to levels similar to those in the NC group. (b) PCA cluster analysis. (c) cluster analysis. (d) Trend gene heat map.
Figure 2
Figure 2
Trend validation and trend gene pathway analysis. (a) Verification of IL-36G by qPCR. (b) Verification of LINC01176 by qPCR. (c) Verification of mir-218-5p by qPCR. (d) GO BP pathway analysis. (e) KEGG pathway analysis (*P < 0.05, **P < 0.01, ***P < 0.001.).
Figure 3
Figure 3
The network of LINCRNA-miRNA regulating IL-36G.
Figure 4
Figure 4
Hsa_linc_01176 targets miR-218-5p affect downstream IL-36G. (a) The binding site of mir-218-5p in LINC01176 3 “-UTR. (b) The binding sites of mir-218-5p in IL36G 3”-UTR. (c and d) Dual-luciferase reporter gene detection showed that mir-218-5p mimics inhibited the luciferase activity of LINC01176-WT and IL-36G-WT reporter molecules. (e and f) The results of qPCR showed that LINC01176 regulated the expression of IL-36G by inhibiting mir-218-5p (*P < 0.05, **P < 0.01, ***P < 0.001.).
Figure 5
Figure 5
miR-218-5p and LINCRNA 01176 had opposite effects on HaCaT cells. (a) CCK8 results showed that LINC01176 promoted the proliferation of HaCaT cells, and mir-218-5p inhibited the proliferation of HaCaT cells. (b–e) Flow cytometry showed that LINC01176 inhibited the apoptosis of HaCaT cells, and mir-218-5p promoted the apoptosis of HaCaT cells (*P < 0.05, **P < 0.01, ***P < 0.001.).
Figure 6
Figure 6
The phenotype and pathology of psoriasis mouse model. (a) Interference with linc01176 has a therapeutic effect on psoriasis model mice. (b) HE staining showed that the extent of lesion repair after interference with LINC01176 approximated that of the NC group, the scale in the figures is 200:1. (c) Immunohistochemical results showed that IL-36G expression after interference with LINC01176 approximated that of the NC group, the scale in the figures is 200:1. (d) qPCR results showed that interference with LINC01176 decreased the gene expression levels of inflammatory factors IL-17, IL-23, and TNF-α in a mouse model of psoriasis (*P < 0.05, **P < 0.01, ***P < 0.001.).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Langley RG, Krueger GG, Griffiths C. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheumatic Dis. 2005;64(suppl 2):ii18–23. doi:10.1136/ard.2004.033217 - DOI - PMC - PubMed
    1. Kamiya K, Kishimoto M, Sugai J, Komine M, Ohtsuki M. Risk factors for the development of psoriasis. Int J Mol Sci. 2019;20(18):4347. doi:10.3390/ijms20184347 - DOI - PMC - PubMed
    1. Armstrong AW, Mehta MD, Schupp CW, Gondo GC, Bell SJ, Griffiths CEM. Psoriasis prevalence in adults in the United States. JAMA dermatol. 2021;157(8):940–946. doi:10.1001/jamadermatol.2021.2007 - DOI - PMC - PubMed
    1. Krueger G, Koo J, Fau - Lebwohl M, et al. The impact of psoriasis on quality of life: results of a 1998 national psoriasis foundation patient-membership survey. Arch Dermatol. 2001;137(3):280–284. - PubMed
    1. Kurd SK, Robert PD, Daihung DO, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 2010;146(8):891–895. doi:10.1001/archdermatol.2010.186 - DOI - PMC - PubMed

Grants and funding

This work was supported by the Major Project of Shanghai Xuhui District Medical Research Fund (grant number SHXH202002), the General Project of Shanghai Science and Technology Commission (grant number 20ZR1432100), Medical Education Collaborative Innovation Foundation of Jiangsu University (grant number JDYY2023093), the Jiangsu University Medical Education Collaborative Innovation Fund (grant number JDYY2023093).

LinkOut - more resources