Complementary Strand MicroRNAs Mediate Acquisition of Metastatic Potential in Colonic Adenocarcinoma

• Published in: Journal of gastrointestinal surgery Vol. 16; no. 5; pp. 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: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.05.2012; Springer Nature B.V
• 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; United States > US; Complementary strand microRNA; Metastates; Colon cancer
• ISSN: 1091-255X; 1873-4626; 1873-4626
• DOI: 10.1007/s11605-011-1815-0

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.