Allergy, Inflammation & Remodelling Research Laboratory, Department of Biology, Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland.
National Esophageal and Gastric Centre, St. James's Hospital Dublin and Trinity St. James's Cancer Institute, Dublin, Ireland.
Am J Physiol Gastrointest Liver Physiol. 2023 Jul 1;325(1):G1-G13. doi: 10.1152/ajpgi.00184.2022. Epub 2023 May 2.
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.
微小 RNA(miRNAs)是一类长约 18-25 个核苷酸的小型内源性 RNA 分子。miRNAs 的主要功能是通过 RNA 干扰对 mRNA 靶标进行转录后调控,最终导致 mRNA 降解或翻译抑制。miRNAs 在细胞增殖、分化、凋亡和炎症等生理和病理过程中起着至关重要的作用。其中包括 miRNA 在整个食管疾病中的潜在作用,特别是在临床病理变态反应性疾病嗜酸粒细胞性食管炎(EoE)、胃食管反流病(GERD)以及从 Barrett 食管(BE)向食管腺癌(EAC)的肿瘤发生连续体中。尽管这些病理情况彼此不同,但它们具有共同的病理生理特征,如强烈的炎症环境、食管功能障碍,以及本综述中提出的 miRNA 表达重叠,这些都有助于整体食管疾病的发生。这些病理情况中失调 miRNA 转录组的重叠突出了 miRNA 在促进食管疾病进展中所起的关键作用。由于这种明显的失调,miRNAs 作为食管疾病的诊断和预后生物标志物具有很大的应用潜力,而这些疾病已经需要进行有创性内窥镜检查和活检获取。本综述讨论了 EoE、GERD、BE、EAC 和食管失弛缓症中的 miRNAs,以及这些病理情况中一些共同的疾病进展中共享的核心 miRNA 集,以及靶向 miRNAs 作为整体食管疾病治疗选择的潜在应用。