Novel specific microRNA biomarkers in idiopathic inflammatory bowel disease unrelated to disease activity.
The diagnosis of idiopathic inflammatory bowel disease can be challenging. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate protein synthesis through post-transcriptional suppression. This study is to identify new miRNA markers in inflammatory bowel disease, and to examine whether miRNA biomarkers might assist in the diagnosis of inflammatory bowel disease. Illumina small RNA sequencing was performed on non-dysplastic fresh-frozen colonic mucosa samples of the distalmost colectomy tissue from 19 patients with inflammatory bowel disease (10 ulcerative colitis and 9 Crohn disease) and 18 patients with diverticular disease serving as controls. To determine differentially expressed miRNAs, the USeq software package identified 44 miRNAs with altered expression (fold change ≥ 2 and false discovery rate ≤ 0.10) compared with the controls. Among them, a panel of nine miRNAs was aberrantly expressed in both ulcerative colitis and Crohn disease. Validation assays performed using quantitative reverse transcription PCR (qRT-PCR) on additional frozen tissue from ulcerative colitis, Crohn disease, and control groups confirmed specific differential expression in inflammatory bowel disease for miR-31, miR-206, miR-424, and miR-146a (P<0.05). The expression of these four miRNAs was further evaluated on formalin-fixed, paraffin-embedded tissue of the distalmost colectomy mucosa from cohorts of diverticular disease controls (n=29), ulcerative colitis (n=36), Crohn disease (n=26), and the other diseases mimicking inflammatory bowel disease including infectious colitis (n=12) and chronic ischemic colitis (n=19), again confirming increased expression specific to inflammatory bowel disease (P<0.05). In summary, we demonstrate that miR-31, miR-206, miR-424, and miR-146a are novel specific biomarkers of inflammatory bowel disease. Furthermore, miR-31 is universally expressed in both ulcerative colitis and Crohn disease not only in fresh-frozen but also in formalin-fixed, paraffin-embedded tissues.
Department of Pathology and Laboratory Medicine, Indianapolis, IN, USA.
Jingmei
J
Lin
Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT, USA.
Noah C
NC
Welker
Department of Pathology and Laboratory Medicine, Indianapolis, IN, USA.
Zijin
Z
Zhao
Department of Pathology and Laboratory Medicine, Indianapolis, IN, USA.
Yong
Y
Li
Department of Public Health, Indianapolis, IN, USA.
Jianjun
J
Zhang
Department of Pathology and Laboratory Medicine, Indianapolis, IN, USA.
Sarah A
SA
Reuss
Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
Xinjun
X
Zhang
Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
Hwajeong
H
Lee
Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
Yunlong
Y
Liu
Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT, USA.
Mary P
MP
Bronner
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000235:genetics*; D003424:Crohn Disease / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D012720:Severity of Illness Index; D055815:Young Adult
D005819:Genetic Markers; C542542:MIRN146 microRNA, human; C546087:MIRN206 microRNA, human; C534612:MIRN31 microRNA, human; C554214:MIRN424 microrna, human; D035683:MicroRNAs