Dynamic changes in the expression of MicroRNA-31 during inflammatory bowel disease-associated neoplastic transformation

Alexandru V. Olaru, Florin M. Selaru, Yuriko Mori, Christine Vazquez, Stefan David, Bogdan Paun, Yulan Cheng, Zhe Jin, Jian Yang, Rachana Agarwal, John M. Abraham, Themistocles Dassopoulos, Mary Harris, Theodore M. Bayless, John Kwon, Noam Harpaz, Ferenc Livak, Stephen J. Meltzer

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer. Aberrant microRNA (miR) expression has been linked to carcinogenesis; however, no reports document a relationship between IBD-related neoplasia (IBDN) and altered miR expression. In the current study we sought to identify specific miR dysregulation along the normal-inflammation-cancer axis. Methods: miR microarrays and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) were used to detect dysregulated miRs. Receiver operating characteristic curve analysis was employed to test for potential usefulness of miR-31 as a disease marker of IBDNs. In silico prediction analysis, Western blot, and luciferase activity measurement were employed for target identification. Results: Several dysregulated miRs were identified between chronically inflamed mucosae and dysplasia arising in IBD. MiR-31 expression increases in a stepwise fashion during progression from normal to IBD to IBDN and accurately discriminated IBDNs from normal or chronically inflamed tissues in IBD patients. Finally, we identified factor inhibiting hypoxia inducible factor 1 as a direct target of miR-31. Conclusions: Our study reveals specific miR dysregulation as chronic inflammation progresses to dysplasia. MiR-31 expression levels increase with disease progression and accurately discriminates between distinct pathological entities that coexist in IBD patients. The novel effect of miR-31 on regulating factor inhibiting hypoxia inducible factor 1 expression provides a new insight on the pathogenesis of IBDN.

Original languageEnglish (US)
Pages (from-to)221-231
Number of pages11
JournalInflammatory bowel diseases
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2011

Keywords

  • IBD-related neoplasia
  • factor inhibiting hypoxia inducible factor 1
  • inflammatory bowel disease
  • microRNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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    Olaru, A. V., Selaru, F. M., Mori, Y., Vazquez, C., David, S., Paun, B., Cheng, Y., Jin, Z., Yang, J., Agarwal, R., Abraham, J. M., Dassopoulos, T., Harris, M., Bayless, T. M., Kwon, J., Harpaz, N., Livak, F., & Meltzer, S. J. (2011). Dynamic changes in the expression of MicroRNA-31 during inflammatory bowel disease-associated neoplastic transformation. Inflammatory bowel diseases, 17(1), 221-231. https://doi.org/10.1002/ibd.21359