Novel MicroRNA Signature to Differentiate Ulcerative Colitis from Crohn Disease: A Genome-Wide Study Using Next Generation Sequencing
2017
Background: The diagnosis of ulcerative colitis (UC) or Crohn disease (CD) can be challenging
given the overlapping features. Knowledge of microRNAs in IBD has expanded recently and
supports that microRNAs play an important role. This study aimed to identify novel microRNA biomarkers
through comprehensive genome-wide sequencing to distinguish UC from CD.
Design: Illumina next generation sequencing was performed on nondysplastic fresh-frozen colonic mucosa
of the distal-most colectomy from 19 patients (10 UC and 9 CD) and 18 patients with diverticular
disease serving as controls.
Results: USeq software package identified 44 microRNAs with altered expression (fold change ≥2 and
false discovery rate ≤0.10) compared to controls. Among them, a panel of 11 microRNAs was aberrantly
expressed between UC and CD. qRT-PCR validation assays performed on frozen tissue from additional
samples of UC (n=20) and CD (n=10) confirmed specific differential expression of miR-147b,
miR-194-2, miR-383, miR-615 and miR-1826 (P<0.05). In addition, pathway analysis identified target
genes of epithelial adhesion junction, integrin, glycolysis and cell cycle that involve in signaling pathways
of TGF-β, STAT3, IL-8 and PI3L/AKT/mTOR.
Conclusion: Identification of differentially expressed microRNAs in UC and CD supports the
hypothesis that UC and CD are regulated by distinct pathophysiologic mechanisms. MicroRNA panels
show promise as diagnostic biomarkers for the subtyping of inflammatory bowel disease.
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