Clinical Bioinformatics Research Group, Department of Clinical Medicine, UiT-The Arctic University of Norway, N-9037 Tromsø, Norway.
Genomic Support Centre Tromsø (GSCT), Department of Clinical Medicine, UiT-The Arctic University of Norway, N-9037 Tromsø, Norway.
Int J Mol Sci. 2023 Jun 22;24(13):10500. doi: 10.3390/ijms241310500.
Long non-coding RNAs (lncRNAs) have been shown to play a role in the pathogenesis of ulcerative colitis (UC). Although epigenetic processes such as DNA methylation and lncRNA expression are well studied in UC, the importance of the interplay between the two processes has not yet been fully explored. It is, therefore, believed that interactions between environmental factors and epigenetics contribute to disease development. Mucosal biopsies from 11 treatment-naïve UC patients and 13 normal controls were used in this study. From each individual sample, both whole-genome bisulfite sequencing data (WGBS) and lncRNA expression data were analyzed. Correlation analysis between lncRNA expression and upstream differentially methylated regions (DMRs) was used to identify lncRNAs that might be regulated by DMRs. Furthermore, proximal protein-coding genes associated with DMR-regulated lncRNAs were identified by correlating their expression. The study identified UC-associated lncRNAs such as MIR4435-2HG, ZFAS1, IL6-AS1, and Pvt1, which may be regulated by DMRs. Several genes that are involved in inflammatory immune responses were found downstream of DMR-regulated lncRNAs, including SERPINB1, CCL18, and SLC15A4. The interplay between lncRNA expression regulated by DNA methylation in UC might improve our understanding of UC pathogenesis.
长链非编码 RNA（lncRNA）已被证明在溃疡性结肠炎（UC）的发病机制中发挥作用。尽管 DNA 甲基化和 lncRNA 表达等表观遗传过程在 UC 中得到了很好的研究，但这两个过程之间相互作用的重要性尚未得到充分探索。因此，人们认为环境因素和表观遗传学之间的相互作用有助于疾病的发展。本研究使用了 11 名未经治疗的 UC 患者和 13 名正常对照的黏膜活检样本。对每个个体样本进行全基因组亚硫酸氢盐测序数据（WGBS）和 lncRNA 表达数据的分析。通过分析 lncRNA 表达与上游差异甲基化区域（DMR）之间的相关性，确定可能受 DMR 调控的 lncRNA。此外，通过关联其表达，确定与 DMR 调控 lncRNA 相关的近端蛋白编码基因。该研究确定了 UC 相关的 lncRNA，如 MIR4435-2HG、ZFAS1、IL6-AS1 和 Pvt1，它们可能受 DMR 调控。在 DMR 调控的 lncRNA 下游发现了几个参与炎症免疫反应的基因，包括 SERPINB1、CCL18 和 SLC15A4。在 UC 中由 DNA 甲基化调控的 lncRNA 表达的相互作用可能会提高我们对 UC 发病机制的理解。
