Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma.

Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract
Dung-Tsa ChenTimothy Yeatman

Abstract

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. 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. 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. We have identified a seven-miRNA signature that is associated with metastatic potential in the primary tumor. Forced overexpression ...Continue Reading

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