Lay Summary

Proposal No. IBD-0271R
Principal Investigator:  Alexandru Olaru, M.D.
Applicant Organization:  Johns Hopkins University (Baltimore, Maryland, U.S.A.)
Project Title:  The role of microRNA alterations in IBD-related neoplasia
Period of Award:  July 1, 2009 – January 31, 2012

Chronic idiopathic inflammatory bowel disease (IBD) predisposes to the development of colorectal carcinoma. Precancerous dysplastic lesions still escape detection. Morphologic alterations associated with chronic inflammation make dysplasia difficult to diagnose and prone to subjective interpretation. In addition, sporadic colorectal adenomas and adenocarcinomas may also develop in the setting of IBD. Distinguishing between IBD-caused dysplasia or neoplasia and sporadic adenoma or carcinoma is essential, since one diagnosis warrants total colectomy while the other can be treated with local excision.

MicroRNAs (miRs) are a recently discovered class of small non-coding RNA. Most known functions of miRs relate to negative gene regulation. While involvement of miRs in several human cancers has been demonstrated, the relationship between aberrant miR expression and IBD-neoplasia has not been explored to date.

We will attempt to prove that in IBDN, expression levels of particular miRs are changing from normal to chronic inflammation to dysplasia to cancer lesions in a stepwise progressive manner. Discovery of such miRs may lead to an improved set of molecular markers with impact in earlier detection and more accurate diagnosis. Similarly, this project will seek to identify miR expression patterns that distinguish sporadic adenomas and cancers from those specific to IBDN. Finally, by identifying the target genes of dysregulated miRs we will also provide new insights into pathways that underlie IBD-associated neoplastic transformation, leading to better disease models and ultimately, to better prevention and intervention.