Complementary Strand MicroRNAs Mediate Acquisition of Metastatic Potential in Colonic Adenocarcinoma

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 eva...

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Bibliographic Details
Published in:Journal of gastrointestinal surgery 2012-05, Vol.16 (5), p.905-913
Main Authors: Chen, Dung-Tsa, Hernandez, Jonathan M., Shibata, David, McCarthy, Susan M., Humphries, Leigh Ann, Clark, Whalen, Elahi, Abul, Gruidl, Mike, Coppola, Domenico, Yeatman, Timothy
Format: Article
Language:English
Subjects:
2011 SSAT Plenary Presentation
Adenocarcinoma
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Adenocarcinoma - surgery
Aged
Algorithms
Biomarkers, Tumor - genetics
Carcinogenesis
Cell Transformation, Neoplastic - genetics
Colectomy - methods
Colon cancer
Colonic Neoplasms - genetics
Colonic Neoplasms - pathology
Colonic Neoplasms - surgery
Colorectal cancer
Down-Regulation
Female
Gastroenterology
Gene Expression Regulation, Neoplastic
Humans
Invasiveness
Male
Medicine
Medicine & Public Health
Metastases
Metastasis
MicroRNAs
MicroRNAs - analysis
Middle Aged
miRNA
Mortality
Neoplasm Invasiveness
Neoplasm Staging
Real-Time Polymerase Chain Reaction - methods
Regulation
Research centers
RNA
RNA polymerase
Sampling Studies
Sensitivity and Specificity
Surgery
Tissue Culture Techniques
Tumor cell lines
Tumors
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Summary: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.
ISSN:1091-255X
1873-4626
DOI:10.1007/s11605-011-1815-0