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Long Non-Coding RNA Signatures in the Ileum and Colon of Crohn's Disease Patients and Effect of Anti-TNF-α Treatment
Montse Baldan-Martin1, Cristina Rubín de Célix1, Macarena Orejudo1
1Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28006 Madrid, Spain.
Abstract:
Biological therapies only benefit one-third of patients with Crohn's disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome.
Insights
Long noncoding RNAs (lncRNAs) show distinct expression patterns in the ileum and colon of Crohn's disease (CD) patients. Anti-TNF-α therapy did not alter lncRNA profiles in this study.
Area of Science:
- Gastroenterology
- Molecular Biology
- Genomics
Background:
- Biological therapies benefit only a minority of Crohn's disease (CD) patients, necessitating a deeper understanding of treatment mechanisms.
- Long noncoding RNAs (lncRNAs) are implicated in CD pathogenesis, but their specific roles and responses to therapy are not well-defined.
Purpose of the Study:
- To characterize lncRNA expression profiles in the ileum and colon of CD patients.
- To investigate the impact of anti-TNF-α treatment on lncRNA transcription in CD.
Main Methods:
- RNA sequencing of terminal ileum and left colon biopsies from 30 patients (active CD, quiescent CD, and healthy controls).
- Transcriptome analysis of patient-derived biopsies cultured with infliximab.
- Classification of patients based on endoscopic disease activity.
Main Results:
- Significant differences in lncRNA expression were observed between the ileum and colon in healthy controls and CD patients.
- CD presence and disease activity were associated with differential lncRNA expression profiles.
- Infliximab treatment did not significantly alter the lncRNA transcriptome, irrespective of intestinal location or disease status.
Conclusions:
- lncRNA expression is significantly influenced by intestinal location and CD status.
- Current anti-TNF-α therapy (infliximab) does not appear to modulate the lncRNA transcriptome in CD patients.
- Further research is needed to elucidate the precise role of lncRNAs in CD pathogenesis and therapeutic response.
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