Microsatellite instability (MSI) due to mismatch repair (MMR) deficiency is 
reported in 5-10% of colorectal cancers (CRCs) complicating inflammatory bowel 
diseases (IBD). The molecular mechanisms underlying MMR deficiency may be 
different in IBD CRCs, and in sporadic and hereditary MSI tumors. Here, we 
hypothesize that overexpression of miR-155 and miR-21, two inflammation-related 
microRNAs that target core MMR proteins, may constitute a pre-neoplastic event 
for the development of MSI IBD CRCs. We studied miR-155 and miR-21 expression 
using real-time quantitative PCR in MSI (n = 10) and microsatellite stable (n = 
10) IBD CRCs, and in MSI (n = 32) and microsatellite stable (n = 30) non-IBD 
CRCs. We also screened colonic samples from IBD patients without cancer (n = 18) 
and used healthy colonic mucosa as controls (n = 20). MiR-155 and miR-21 
appeared significantly overexpressed not only in the colonic mucosa of IBD 
subjects without CRC but also in neoplastic tissues of IBD patients compared 
with non-IBD controls (P < 0.001). Importantly, in patients with IBD CRCs, 
miR-155 and miR-21 overexpression extended to the distant non-neoplastic mucosa 
(P < 0.001). Ratios of expressions in tumors versus matched distant mucosa 
revealed a nearly significant association between miR-155 overexpression and MSI 
in IBDs (P = 0.057). These results show a strong deregulation of both 
MMR-targeting microRNAs in IBD subjects with or without cancer. MiR-155 
overexpression being particularly associated to MSI IBD CRCs and extending to 
distant non-neoplastic mucosa, strongly suggests that a pre-neoplastic miR-155 
field defect may promote MSI-driven transformation of the colonic mucosa. The 
detection and monitoring of miR-155 field defect may, therefore, have 
implications for the prevention and treatment of MSI IBD CRCs.