Common MicroRNA Biomarkers To Characterize Inflammatory Bowel Disease
Jingmei Lin, Zijin Zhao, Noah C Welker, Yunlong Liu, Xinjun Zhang, Jianjun Zhang, Yong Li, Hwa-Jeong Lee, Mary P Bronner. Indiana University School of Medicine, Indianapolis, IN; University of Utah, Salt Lake City, UT; Albany Medical Center, Albany, NY
Background: The pathogenesis of idiopathic inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn disease (CD), is integrated from genetic, epigenetic, and environmental factors. The pathologic diagnosis of IBD can be challenging if the patient presents with fulminant colitis. MicroRNAs (miRNAs) are small, noncoding RNAs, which regulate the physiological processes by preventing protein synthesis through posttranscriptional suppression.
Design: This study examines whether common miRNA biomarkers of IBD can be identified and whether they might assist in diagnosing IBD. Illumina small RNA sequencing was performed on nondysplastic fresh-frozen colonic mucosa samples from patients with a diagnosis of IBD (10 UC and 9 CD) and from 18 patients with diverticular disease as “normal” controls.
Results: USeq software was used to identify 9 miRNAs with altered expression in both UC and CD (fold change, ≥2; false discovery rate, ≤0.10) compared to normal controls. Validation assays were performed using qRT-PCR on frozen tissue to confirm the altered expression of four of them (mir-31, mir-206, mir-424 and mir-146a) (P<0.05). Furthermore, the expression of these four microRNAs was evaluated on the formalin-fixed, paraffin-embedded tissue from cohorts of diverticular disease controls (n=15), UC (n=35), CD (n=21) and other diseases that mimic IBD including colonic infection (n=12) and ischemia (n=12). The expression of mir-31 was significantly increased in IBD groups compared to the control and the infections groups (P<0.05).
Conclusions: Our study indicates that mir-31 is commonly expressed in both UC and CD, regardless of the status of inflammation. Furthermore, mir-31 could be used as a valuable ancillary biomarker to diagnose IBD in either fresh-frozen tissue or routinely used formalin-fixed, paraffin-embedded tissue.
Monday, March 4, 2013 1:00 PM
Poster Session II # 262, Monday Afternoon