{"title":"Comprehensive analysis and validation of autophagy-related gene in rheumatoid arthritis.","authors":"Runrun Zhang, Wenhan Huang, Ting Zhao, Jintao Fang, Cen Chang, Dongyi He, Xinchang Wang","doi":"10.3389/fcell.2025.1563911","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic autoimmune disease in which autophagy is pivotal in its pathogenesis. This study aims to identify autophagy-related genes associated with RA and investigate their functional roles.</p><p><strong>Methods: </strong>We performed mRNA sequencing to identify differentially expressed genes (DEGs) between RA and osteoarthritis (OA) and intersected these with autophagy-related genes to obtain autophagy-related DEGs (ARDEGs) in RA. Bioinformatics and machine learning approaches were used to identify key biomarkers. Functional experiments, including real-time cellular analysis (RTCA), scratch healing, and flow cytometry, were conducted to examine the effects of gene silencing on the proliferation and migration of MH7A cells.</p><p><strong>Results: </strong>A total of 37 ARDEGs were identified in RA. Through bioinformatics analysis, interferon regulatory factor 4 (IRF4) emerged as a key hub gene, with its high expression confirmed in RA synovial tissues and RA FLS cells. IRF4 knockdown inhibited the proliferation and migration and promoted the death of MH7A cells.</p><p><strong>Conclusion: </strong>IRF4 is an autophagy-related diagnostic biomarker for RA. Targeting IRF4 could serve as a potential diagnostic and therapeutic strategy for RA, although further clinical studies are required to validate its effectiveness.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1563911"},"PeriodicalIF":4.6000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965638/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cell and Developmental Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fcell.2025.1563911","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease in which autophagy is pivotal in its pathogenesis. This study aims to identify autophagy-related genes associated with RA and investigate their functional roles.
Methods: We performed mRNA sequencing to identify differentially expressed genes (DEGs) between RA and osteoarthritis (OA) and intersected these with autophagy-related genes to obtain autophagy-related DEGs (ARDEGs) in RA. Bioinformatics and machine learning approaches were used to identify key biomarkers. Functional experiments, including real-time cellular analysis (RTCA), scratch healing, and flow cytometry, were conducted to examine the effects of gene silencing on the proliferation and migration of MH7A cells.
Results: A total of 37 ARDEGs were identified in RA. Through bioinformatics analysis, interferon regulatory factor 4 (IRF4) emerged as a key hub gene, with its high expression confirmed in RA synovial tissues and RA FLS cells. IRF4 knockdown inhibited the proliferation and migration and promoted the death of MH7A cells.
Conclusion: IRF4 is an autophagy-related diagnostic biomarker for RA. Targeting IRF4 could serve as a potential diagnostic and therapeutic strategy for RA, although further clinical studies are required to validate its effectiveness.
期刊介绍:
Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board.
The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology.
With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.