Circ_0060531 knockdown ameliorates IL-22-induced keratinocyte damage by binding to miR-330-5p to decrease GAB1 expression

Background Psoriasis is a chronic immune-mediated skin disease. Recent studies showed its pathogenesis involved circular RNA (circRNA). However, the role of circ_0060531 in psoriasis development and the behind mechanism remain to be explored. Methods Psoriasis cell model was constructed by treating...

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Main Authors: Quan Shi, Jing Luo, Weiming Chen, Qi He, Jianwen Long, Bo Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2022-05-01
Series:Autoimmunity
Subjects:
Online Access:http://dx.doi.org/10.1080/08916934.2022.2037127
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author Quan Shi
Jing Luo
Weiming Chen
Qi He
Jianwen Long
Bo Zhang
author_facet Quan Shi
Jing Luo
Weiming Chen
Qi He
Jianwen Long
Bo Zhang
author_sort Quan Shi
collection DOAJ
description Background Psoriasis is a chronic immune-mediated skin disease. Recent studies showed its pathogenesis involved circular RNA (circRNA). However, the role of circ_0060531 in psoriasis development and the behind mechanism remain to be explored. Methods Psoriasis cell model was constructed by treating keratinocytes (HaCaT cells) using interleukin 22 (IL-22). Expression of circ_0060531, microRNA-330-5p (miR-330-5p) and GRB2 associated binder 1 (GAB1) was determined by quantitative real-time polymerase chain reaction. The functional effects of circ_0060531 on IL-22-caused cell injury were investigated by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-Ethynyl-29-deoxyuridine, wound-healing and enzyme-linked immunosorbent assays. Protein expression was analysed by Western blot. The interactions among circ_0060531, miR-330-5p and GAB1 were identified by dual-luciferase reporter or RNA immunoprecipitation assay. Results Circ_0060531 and GAB1 expression were significantly increased, while miR-330-5p was decreased in psoriatic skin biopsies and IL-22-stimulated HaCaT cells in comparison with controls. In function, circ_0060531 knockdown assuaged IL-22-induced cell proliferation, cell migration and inflammation. Besides, circ_0060531 acted as a miR-330-5p sponge, and regulated the processes of IL-22-treated HaCaT cells by binding to the miRNA. Under the treatment of IL-22, miR-330-5p mediated HaCaT cell damage by targeting GAB1. Importantly, circ_0060531 modulated GAB1 production by interacting with miR-330-5p. Conclusion Circ_0060531 knockdown assuaged IL-22-induced keratinocyte dysfunction through miR-330-5p/GAB1 pathway, proving a novel target for the therapy of psoriasis.
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spelling doaj.art-45d39717e23a459ebd90eb2d5fe17eed2023-09-15T10:12:24ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2022-05-0155424325310.1080/08916934.2022.20371272037127Circ_0060531 knockdown ameliorates IL-22-induced keratinocyte damage by binding to miR-330-5p to decrease GAB1 expressionQuan Shi0Jing Luo1Weiming Chen2Qi He3Jianwen Long4Bo Zhang5Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese MedicineDepartment of Dermatology, Hubei Provincial Hospital of Traditional Chinese MedicineDepartment of Dermatology, Hubei Provincial Hospital of Traditional Chinese MedicineDepartment of Dermatology, Hubei Provincial Hospital of Traditional Chinese MedicineDepartment of Dermatology, Hubei Provincial Hospital of Traditional Chinese MedicineDepartment of Dermatology, Hubei Provincial Hospital of Traditional Chinese MedicineBackground Psoriasis is a chronic immune-mediated skin disease. Recent studies showed its pathogenesis involved circular RNA (circRNA). However, the role of circ_0060531 in psoriasis development and the behind mechanism remain to be explored. Methods Psoriasis cell model was constructed by treating keratinocytes (HaCaT cells) using interleukin 22 (IL-22). Expression of circ_0060531, microRNA-330-5p (miR-330-5p) and GRB2 associated binder 1 (GAB1) was determined by quantitative real-time polymerase chain reaction. The functional effects of circ_0060531 on IL-22-caused cell injury were investigated by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-Ethynyl-29-deoxyuridine, wound-healing and enzyme-linked immunosorbent assays. Protein expression was analysed by Western blot. The interactions among circ_0060531, miR-330-5p and GAB1 were identified by dual-luciferase reporter or RNA immunoprecipitation assay. Results Circ_0060531 and GAB1 expression were significantly increased, while miR-330-5p was decreased in psoriatic skin biopsies and IL-22-stimulated HaCaT cells in comparison with controls. In function, circ_0060531 knockdown assuaged IL-22-induced cell proliferation, cell migration and inflammation. Besides, circ_0060531 acted as a miR-330-5p sponge, and regulated the processes of IL-22-treated HaCaT cells by binding to the miRNA. Under the treatment of IL-22, miR-330-5p mediated HaCaT cell damage by targeting GAB1. Importantly, circ_0060531 modulated GAB1 production by interacting with miR-330-5p. Conclusion Circ_0060531 knockdown assuaged IL-22-induced keratinocyte dysfunction through miR-330-5p/GAB1 pathway, proving a novel target for the therapy of psoriasis.http://dx.doi.org/10.1080/08916934.2022.2037127psoriasiscirc_0060531mir-330-5pgab1
spellingShingle Quan Shi
Jing Luo
Weiming Chen
Qi He
Jianwen Long
Bo Zhang
Circ_0060531 knockdown ameliorates IL-22-induced keratinocyte damage by binding to miR-330-5p to decrease GAB1 expression
Autoimmunity
psoriasis
circ_0060531
mir-330-5p
gab1
title Circ_0060531 knockdown ameliorates IL-22-induced keratinocyte damage by binding to miR-330-5p to decrease GAB1 expression
title_full Circ_0060531 knockdown ameliorates IL-22-induced keratinocyte damage by binding to miR-330-5p to decrease GAB1 expression
title_fullStr Circ_0060531 knockdown ameliorates IL-22-induced keratinocyte damage by binding to miR-330-5p to decrease GAB1 expression
title_full_unstemmed Circ_0060531 knockdown ameliorates IL-22-induced keratinocyte damage by binding to miR-330-5p to decrease GAB1 expression
title_short Circ_0060531 knockdown ameliorates IL-22-induced keratinocyte damage by binding to miR-330-5p to decrease GAB1 expression
title_sort circ 0060531 knockdown ameliorates il 22 induced keratinocyte damage by binding to mir 330 5p to decrease gab1 expression
topic psoriasis
circ_0060531
mir-330-5p
gab1
url http://dx.doi.org/10.1080/08916934.2022.2037127
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