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microRNA

mRNA

Translational repression or degradation of mRNA

Protein synthesis

Figure 2. Post-transcriptional regulation of target mRNAs by microRNAs. microRNAs bind to complementary sequences on target
messenger RNAs and promote degradation of the nascent transcript before it can be translated into protein

However, to date only three studies have reported on miRNA expression in EoE and fewer still have com-
mented on the function of miRNAs in eosinophilic esophagitis pathogenesis. This review discusses our
current understanding of miRNA roles in eosinophilic esophagitis, offers insights into miRNA potential for
clinical utility, and comments on future investigations.

MIRNA CONTRIBUTIONS TO NORMAL ESOPHAGEAL FUNCTION
First identified in 1977, EoE was originally thought to be a variant of gastroenteritis and was only later iden-
tified as a distinct clinical entity . Nearly three decades later, microRNAs were unearthed as immunoregu-
[27]
latory molecules and pathogenic contributors to the inflammation in EoE. miRNAs are small noncoding
RNAs, approximately 12-22 nucleotides in length, that participate in post-transcriptional gene silencing of
targets. Binding of miRNAs with complementary base pairs in the 3’ untranslated region (UTR) of mRNA
transcripts leads to inhibition of target gene expression or protein [Figure 2].

miRNAs have homeostatic roles in normal cellular processes in all cells and tissues. In the gastrointestinal
epithelium, miRNAs have been shown to regulate aspects of mucosal immunity and barrier response [28,29] .
For example, miR-34a and miR-365 have roles in the maturation of gut-associated lymphoid tissue (GALT).
miR-34a has been shown to downregulate members of the Notch1 signaling pathway that control normal
differentiation of M cells, a highly specialized epithelial cell . In this way, repression of Notch-1 signal-
[30]
ing by miR-34a leads to normal development of structures at the mucosal interface that sample antigen and
initiate immune responses. Likewise, repression of miR-365’s target gene, Myb-related protein B (MYBL2)
is necessary for colonic epithelium to fully differentiate. Deregulation of miRNA pathways or alterations in
miRNA expression in tissue can then perturb homeostasis and lead to disease conditions like eosinophilic
inflammation in the esophagus.

DYSREGULATION OF MIRNAS IN INFLAMED TISSUE DIFFERENTIATES EOE FROM HEALTHY
ESOPHAGI
In 2012, Lu et al. uncovered the first evidence of a unique, miRNA signature in diseased esophageal tissue
[31]