PDF(Pubmed)
Abstract：
BACKGROUND: N6-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.
METHODS: The 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).
RESULTS: The 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.
CONCLUSIONS: In 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.
METHODS: The 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).
RESULTS: The 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.
CONCLUSIONS: In 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.
摘要：
背景：N6-甲基腺苷（m6A）已被鉴定为RNA分子的最丰富修饰，并且异常的m6A修饰与自身免疫性疾病的发展有关。然而,m6A修饰在强直性脊柱炎(AS)中的作用尚未得到充分研究.因此,我们旨在探讨m6A调节因子介导的RNA甲基化在AS中的意义。
方法：使用来自3例AS患者和3例健康对照者的外周血单核细胞进行甲基化RNA免疫沉淀测序（meRIP-seq）和数字RNA测序（DigitalRNA-seq），鉴定受异常RNA甲基化影响的基因。将与不同峰相关的基因与从GeneCards套件获得的AS相关基因交叉参考。随后，使用来自两个数据集(GSE25101和GSE73754)的68例AS病例和36例健康对照的数据,评估了AS中共有差异表达基因(DEGs)和关键m6A调节因子的表达水平.此外,结果通过定量聚合酶链反应(qPCR)进行验证.
结果：meRIP-seq和DigitalRNA-seq分析确定了28个基因的m6A峰上调，但表达下调，52个基因的m6A峰下调，但表达上调。通过将与不同峰相关的基因与GeneCardsSuite中的2184个AS相关基因相交，我们总共确定了五个共享DEG：BCL11B，KAT6B,IL1R1、TRIB1和ALDH2。通过对数据集和qPCR的分析,我们发现BCL11B和IL1R1在AS中差异表达。此外，两个关键的M6A调节器，WTAP和异质核核糖核蛋白C，已确定。
结论：结论：目前的研究表明,m6A修饰在AS中起着至关重要的作用,因此可能为AS疾病提供新的治疗策略.
方法：使用来自3例AS患者和3例健康对照者的外周血单核细胞进行甲基化RNA免疫沉淀测序（meRIP-seq）和数字RNA测序（DigitalRNA-seq），鉴定受异常RNA甲基化影响的基因。将与不同峰相关的基因与从GeneCards套件获得的AS相关基因交叉参考。随后，使用来自两个数据集(GSE25101和GSE73754)的68例AS病例和36例健康对照的数据,评估了AS中共有差异表达基因(DEGs)和关键m6A调节因子的表达水平.此外,结果通过定量聚合酶链反应(qPCR)进行验证.
结果：meRIP-seq和DigitalRNA-seq分析确定了28个基因的m6A峰上调，但表达下调，52个基因的m6A峰下调，但表达上调。通过将与不同峰相关的基因与GeneCardsSuite中的2184个AS相关基因相交，我们总共确定了五个共享DEG：BCL11B，KAT6B,IL1R1、TRIB1和ALDH2。通过对数据集和qPCR的分析,我们发现BCL11B和IL1R1在AS中差异表达。此外，两个关键的M6A调节器，WTAP和异质核核糖核蛋白C，已确定。
结论：结论：目前的研究表明,m6A修饰在AS中起着至关重要的作用,因此可能为AS疾病提供新的治疗策略.
