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Erschienen in:
01.05.2012 | 2011 SSAT Plenary Presentation
Complementary Strand MicroRNAs Mediate Acquisition of Metastatic Potential in Colonic Adenocarcinoma
Erschienen in: Journal of Gastrointestinal Surgery | Ausgabe 5/2012
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Background
Altered expression of specific microRNAs (miRNA) is known to occur during colorectal carcinogenesis. However, little is known about the genome-wide alterations in miRNA expression during the neoplastic progression of primary colorectal cancers.
Methods
Using a miRNA array platform, we evaluated the expression of 668 miRNA in primary colonic adenocarcinomas. Biological functions of selected miRNA were evaluated with in vitro invasion assays.
Results
RNA was extracted for miRNA analysis from 65 primary colon cancers. We identified a seven-miRNA expression signature that differentiated stage I and stage IV primary colon cancers. We then demonstrated this signature was able to discriminate between stage II and III primary colon cancers. Six differentially expressed miRNA were downregulated in association with the development of metastases, and all 7 miRNA were complementary strand miRNA. We transfected HCT-116, a highly invasive colon cancer cell line, with corresponding downregulated miRNA and demonstrated that overexpression of three miRNA (miR200c*, miR143*, and miR424*) significantly abrogated invasive potential.
Conclusion
We have identified a seven-miRNA signature that is associated with metastatic potential in the primary tumor. Forced overexpression of three downregulated miRNA resulted in attenuation of in vitro invasion, suggesting direct tumor suppressive function and further supporting the biological importance of complementary strand miRNA.