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MedLine Citation:
PMID:  23288924     Owner:  NLM     Status:  Publisher    
Microsatellite instability (MSI) due to mismatch repair (MMR) deficiency is reported in 5-10% of colorectal cancers complicating inflammatory bowel diseases (IBD-CRCs). The molecular mechanisms underlying MMR-deficiency may be different in IBD-CRCs, and in sporadic and hereditary MSI tumours. Here we hypothesize that over-expression of miR-155 and miR-21, two inflammation-related miRNAs 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 MSS (microsatellite stable, n=10) IBD-CRCs, and in MSI (n=32) and MSS (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 over-expressed in the colonic mucosa of IBD subjects without CRC, but also in neoplastic tissues of IBD patients compared to non-IBD controls (p<0.001). Importantly, in patients with IBD-CRCs, miR-155 and miR-21 over-expression extended to the distant non-neoplastic mucosa (p<0.001). Ratios of expressions in tumours versus matched distant mucosa revealed a nearly significant association between miR-155 over-expression and MSI in IBDs (p=0.057). These results show a strong deregulation of both MMR-targeting miRNAs in IBD subjects with or without cancer. MiR-155 over-expression 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.
Magali Svreck; Nizar El-Murr; Kristell Wanherdrick; Sylvie Dumont; Laurent Beaugerie; Jacques Cosnes; Jean-Frédéric Colombel; Emmanuel Tiret; Jean-François Fléjou; Thécla Lesuffleur; Alex Duval
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-3
Journal Detail:
Title:  Carcinogenesis     Volume:  -     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
INSERM, UMR S 938 - Centre de Recherche Saint-Antoine, Equipe « Instabilité des Microsatellites et Cancers », F-75012, Paris, France.
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