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MicroRNA dysregulation and therapeutic opportunities in esophageal diseases
Gary E Markey1, Claire L Donohoe2, Eóin N McNamee3
1Allergy, Inflammation & Remodelling Research Laboratory, Department of Biology, Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland.
Abstract:
MicroRNAs (miRNAs) are a class of small endogenous RNA molecules between 18 and 25 nucleotides long. The primary function of miRNAs is in the posttranscriptional regulation of mRNA targets through RNA interference culminating in mRNA degradation or translational repression. MiRNAs are fundamental in physiological and pathological processes such as cell proliferation, differentiation, apoptosis, and inflammation. Among this includes the uncovered potential of miRNAs in overall esophageal disease with a focus on the clinicopathologic allergic disease eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), and the tumorigenic continuum from Barrett's esophagus (BE) toward esophageal adenocarcinoma (EAC). Although these pathologies are distinct from one another, they share pathophysiological elements such as an intense inflammatory milieu, esophageal dysfunction, and as presented in this review, an overlap in miRNA expression which contributes to overall esophageal disease. The overlap in the dysregulated miRNA transcriptome of these pathologies highlights the key role miRNAs play in contributing to esophageal disease progression. Owing to this notable dysregulation, there is an attractive utility for miRNAs as diagnostic and prognostic biomarkers in esophageal diseases that already require invasive endoscopies and biopsy retrieval. In this review miRNAs within EoE, GERD, BE, EAC, and esophageal achalasia are discussed, as well as reviewing a core set of miRNAs shared in the disease progression among some of these pathologies, along with the potential utility of targeting miRNAs as therapeutic options in overall esophageal disease.
Insights
MicroRNAs regulate gene expression and are key in esophageal diseases like eosinophilic esophagitis and GERD. Dysregulated miRNAs offer potential as biomarkers for diagnosis and therapy.
Area of Science:
- Molecular Biology
- Genetics
- Gastroenterology
Background:
- MicroRNAs (miRNAs) are small endogenous RNA molecules regulating gene expression post-transcriptionally.
- They play crucial roles in physiological and pathological processes, including inflammation and cell proliferation.
- Esophageal diseases like eosinophilic esophagitis (EoE), GERD, Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) share inflammatory and functional elements.
Purpose of the Study:
- To review the role of miRNAs in various esophageal diseases.
- To highlight the overlapping miRNA expression patterns across distinct esophageal pathologies.
- To explore the potential of miRNAs as diagnostic/prognostic biomarkers and therapeutic targets.
Main Methods:
- Literature review of studies on miRNAs in EoE, GERD, BE, EAC, and achalasia.
- Analysis of shared miRNA dysregulation across these conditions.
- Discussion of miRNA-based diagnostic and therapeutic strategies.
Main Results:
- MiRNAs are fundamentally involved in the pathogenesis of esophageal diseases.
- Significant overlap exists in miRNA expression profiles among EoE, GERD, BE, and EAC.
- Dysregulated miRNAs are implicated in disease progression and shared pathophysiological mechanisms.
Conclusions:
- Shared miRNA dysregulation underscores their critical role in esophageal disease progression.
- MiRNAs represent promising biomarkers for non-invasive diagnosis and prognosis.
- Targeting miRNAs offers a potential therapeutic avenue for esophageal diseases.
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