Department of Orthopedics, Yiwu Central Hospital, Yiwu, China.
Department of Orthopedics, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Immun Inflamm Dis. 2024 Aug;12(8):e1314. doi: 10.1002/iid3.1314.
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.
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).
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.
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.
N6-甲基腺苷（m6A）已被鉴定为 RNA 分子中最丰富的修饰，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 调节剂介导的 RNA 甲基化在 AS 中的意义。
使用来自三个 AS 病例和三个健康对照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（Digital RNA-seq），以鉴定受异常 RNA 甲基化影响的基因。与 AS 相关基因从 GeneCards Suite 中获得，并与不同峰相关的基因进行交叉参考。随后，使用来自两个数据集（GSE25101 和 GSE73754）的 68 个 AS 病例和 36 个健康对照的数据评估共享差异表达基因（DEG）和关键 m6A 调节剂在 AS 中的表达水平。此外，通过定量聚合酶链反应（qPCR）对结果进行验证。
meRIP-seq 和 Digital RNA-seq 分析鉴定了 28 个 m6A 峰上调但表达下调的基因，以及 52 个 m6A 峰下调但表达上调的基因。通过将与不同峰相关的基因与 GeneCards Suite 中 2184 个 AS 相关基因进行交叉参考，我们共鉴定出 5 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 中存在差异表达。此外，还鉴定了两个关键的 m6A 调节剂，WTAP 和异质核核糖核蛋白 C。
总之，本研究揭示了 m6A 修饰在 AS 中起关键作用，因此可能为 AS 疾病提供新的治疗策略。
