Dataset Information

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.

SUBMITTER: Fenton CG

PROVIDER: S-EPMC10341861 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

Fenton Christopher G CG Ray Mithlesh Kumar MK Meng Wei W Paulssen Ruth H RH

International journal of molecular sciences 20230622 13

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 contro ...[more]

PMID: 37445676

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Project description:Long noncoding RNA (lncRNAs) are involved in the pathogenesis of ulcerative colitis (UC). Moxibustion, a traditional Chinese medicine, can improve symptoms in patients with UC and reduce intestinal inflammation in rats with UC. However, it remains unclear whether the ameliorative effect of moxibustion on intestinal mucosal inflammation in UC is related to lncRNAs. Thirty-two rats were randomly assigned to four groups: normal control, UC, moxibustion (MOX), and sulfasalazine (SASP). The UC rat model was induced by administering 4% dextran sulfate sodium (DSS) in drinking water. Rats in the moxibustion group underwent bilateral Tianshu (ST25) moxibustion using the herbs-partition moxibustion method. Rats in the sulfasalazine group received SASP solution via gavage twice daily for seven consecutive days. Our results revealed that, compared with the UC group [2.00 (1.00, 2.50)], the DAI score [0.25 (0.00, 0.50)] was significantly lower in the MOX group (P < 0.05). Compared with the UC group [13.00 (11.25, 14.00)], the histopathological score [5.50 (4.00, 7.75)] was significantly lower in the MOX group (P < 0.05). In addition, the CMDI and macroscopic scores were decreased in the MOX group (P < 0.05). Moxibustion significantly decreased the protein expression of inflammatory factors TNF-α, IFN-γ, and IL-1β in the colonic tissues of UC rats (P <0.05), thereby suppressing the inflammatory response. Moreover, moxibustion exerted a regulatory influence on colon lncRNA and mRNA expression profiles, upregulating LOC108352929 and downregulating Phf11 in rats with UC (P <0.05). Moxibustion also led to a reduction in the expression and colocalization of Phf11 and NF-κB in the colons of UC rats. Moreover, knockdown of LOC108352929 in rat enteric glial cells demonstrated a significant upregulation of TNF-α mRNA expression (P <0.05). In summary, these data illustrate that moxibustion effectively ameliorates DSS-induced colonic injury and inflammation while exerting regulatory control over the lncRNA-mRNA co-expression network in UC rats. Collectively, the in vivo and in vitro studies suggested that LOC108352929-Phf11 may serve as a potential biological marker for moxibustion in the treatment of UC.

Project description:BackgroundUlcerative colitis (UC) is an immune-mediated chronic intestinal disease, with a pathogenesis that remains incompletely understood. The purpose of this study is to analyze the difference of gene expression between UC patients and healthy controls using Oxford Nanopore Technology's long-read RNA sequencing (ONT-RNA-seq) and to explore how alternative polyadenylation (APA) site selection contributes to UC pathogenesis.MethodsColon tissue samples from UC and normal controls (NC) were collected, and total RNA was extracted and sequenced using ONT-RNA-seq technology. Various bioinformatics analyses were performed, including differential expression gene (DEG) analysis, functional enrichment analysis, APA site analysis, and prediction miRNAs and RNA binding proteins (RBPs) targets, to explore the molecular mechanism underlying UC.ResultsONT-RNA-seq analysis revealed that the expression levels of ACSF2, NPY, SLC26A3, BRINP3, and PKLPP2 were significantly lower in UC patients compared to the NC group, while the expression levels of CCL20, CCL21, CD55, IDO1, LCN2, NOS2, CCL11, OLFM4, ANXA1, REG1A, S100A9, SLPI, SPINK1, and AGR2 were significantly higher. Functional enrichment analysis showed that DEGs were closely related to immune and inflammatory responses, which in turn are related to many challenges in the diagnosis and treatment of UC. Mechanistically, APA site selection was found to contribute to the regulation of gene expression in UC, and some APA genes were identified as potential regulators of miRNAs and RBPs. Vene diagram revealed significant overlap between miRNA- and RBP-targeted genes and DEGs, suggesting that APA genes may modulate genes expression in UC through miRNA and RBP targeting. Additionally, five key APA genes--CD38, NCALD, SMIM31, GPX7, and SWAP70--were identified as potentially playing crucial role in UC pathogenesis.ConclusionsThis study provides new insights into the molecular mechanisms of UC through ONT-RNA-seq technology, especially in gene expression regulation and APA site selection.

Dataset Information

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

Publications

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

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