Identification of key genes with abnormal RNA methylation modification and selected m6A regulators in ankylosing spondylitis

作者全名："Wu, Fengqing; Huang, Hongbin; Sun, Deyang; Cai, Bingbing; Zhou, Huateng; Quan, Renfu; Yang, Huan"

作者地址："[Wu, Fengqing] Yiwu Cent Hosp, Dept Orthoped, Yiwu, Peoples R China; [Huang, Hongbin] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped, Chongqing, Peoples R China; [Sun, Deyang] Zhejiang Chinese Med Univ, Coll Clin Med 1, Hangzhou, Peoples R China; [Cai, Bingbing; Zhou, Huateng; Quan, Renfu] Hangzhou Xiaoshan Dist Chinese Med Hosp, Dept Orthoped, Hangzhou, Peoples R China; [Yang, Huan] Zhejiang Univ, Sch Med, Dept Biochem, Hangzhou, Peoples R China; [Yang, Huan] Zhejiang Univ, Med Ctr, Hangzhou, Peoples R China"

通信作者："Quan, RF (通讯作者)，Hangzhou Xiaoshan Dist Chinese Med Hosp, Dept Orthoped, Hangzhou, Peoples R China.; Yang, H (通讯作者)，Zhejiang Univ, Sch Med, Dept Biochem, Hangzhou, Peoples R China.; Yang, H (通讯作者)，Zhejiang Univ, Med Ctr, Hangzhou, Peoples R China."

来源：IMMUNITY INFLAMMATION AND DISEASE

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001282260300001

JCR分区：Q4

影响因子：3.2

年份：2024

卷号：12

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：ankylosing spondylitis; bioinformatics; N6-methyladenosine (m6A); RNA sequence analyses

摘要："BackgroundN6-methyladenosine (m6A) has been identified as the most abundant modification of RNA molecules and the aberrant m6A modifications have been associated with the development of autoimmune diseases. However, the role of m6A modification in ankylosing spondylitis (AS) has not been adequately investigated. Therefore, we aimed to explore the significance of m6A regulator-mediated RNA methylation in AS.MethodsThe methylated RNA immunoprecipitation sequencing (meRIP-seq) and digital RNA sequencing (Digital RNA-seq) were conducted using the peripheral blood mononuclear cells from three AS cases and three healthy controls, to identify genes affected by abnormal RNA methylation. The genes associated with different peaks were cross-referenced with AS-related genes obtained from the GeneCards Suite. Subsequently, the expression levels of shared differentially expressed genes (DEGs) and key m6A regulators in AS were evaluated using data from 68 AS cases and 36 healthy controls from two data sets (GSE25101 and GSE73754). In addition, the results were validated through quantitative polymerase chain reaction (qPCR).ResultsThe meRIP-seq and Digital RNA-seq analyses identified 28 genes with upregulated m6A peaks but with downregulated expression, and 52 genes with downregulated m6A peaks but with upregulated expression. By intersecting the genes associated with different peaks with 2184 AS-related genes from the GeneCards Suite, we identified a total of five shared DEGs: BCL11B, KAT6B, IL1R1, TRIB1, and ALDH2. Through analysis of the data sets and qPCR, we found that BCL11B and IL1R1 were differentially expressed in AS. Moreover, two key m6A regulators, WTAP and heterogeneous nuclear ribonucleoprotein C, were identified.ConclusionsIn conclusion, the current study revealed that m6A modification plays a crucial role in AS and might hence provide a new treatment strategy for AS disease. This article reveals that aberrant expression of m6A regulators contributes to AS development. This relation may be conducted by genes BCL11B and IL1R1, as well as m6A regulators WTAP and HNRNPC. Considering the importance of m6A modification as a critical regulator on AS, blocking or inhibiting certain m6A enzymes may reveal previously unidentified strategies for therapeutic interventions against AS disease. image"

基金机构："Public Platform of Pharmaceutical Research Center, Academy of Chinese Medical Science, Zhejiang Chinese Medical University"

基金资助正文："Public Platform of Pharmaceutical Research Center, Academy of Chinese Medical Science, Zhejiang Chinese Medical University"