Scientific Abstract

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 – December 31, 2010

MicroRNAs (miRs) are single-stranded, 21-23 nucleotide non-coding RNA species that play integral roles in gene regulation. MiR functions are broad, ranging from development and differentiation to proliferation, apoptosis and metabolism. Moreover, altered miR expression has been implicated in tumor initiation and progression in a variety of human cancers. However, thus far, there have been no published reports documenting a relationship between IBDN and miR expression or function. We propose that aberrant microRNA expression contributes to neoplastic transformation in patients with IBD, and that miR expression levels per se can be useful as biomarkers for early detection and disease progression in patients IBDN. We further posit that miR expression levels can be used to discriminate IBDN and IBD-associated dysplastic lesions from sporadic colorectal adenomas and cancers (SACs).

Our preliminary data indicates that there are dramatic differences in the levels of several miRs between non-neoplastic IBD, IBDNs and SACs. In the current proposal, we will evaluate miR expression levels at each stage of neoplastic transformation in IBD to identify a distinct set of dysregulated miRs to guide future IBD patient surveillance and treatment. We will also study these miRs for putative gene targets. Results of these studies will uncover novel carcinogenetic pathways underlying IBDN while simultaneously discovering clinically valuable early diagnostic and prognostic biomarkers.