Methylation-Regulated Long Non-Coding RNA Expression in Ulcerative Colitis

Abstract

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.

Epigenetic regulation and therapeutic strategies in ulcerative colitis

“…A recent study uncovered UC-related lncRNAs, including ZFAS1 , MIR4435-2HG , Pvt1 , and IL6-AS1 , probably regulated by upstream differentially methylated regions (DMRs). And they further identified genes implicated in the inflammatory immune responses downstream of DMR-modulated lncRNAs, including CCL18 , SERPINB1 , and SLC15A4 ( Fenton et al, 2023 ). Therefore, the interplay between the expression of lncRNAs in UC and the regulation of DNA methylation may enhance our knowledge of the immunopathogenesis in UC.…”