Journal of Gastrointestinal Surgery

, Volume 16, Issue 5, pp 905–913 | Cite as

Complementary Strand MicroRNAs Mediate Acquisition of Metastatic Potential in Colonic Adenocarcinoma

  • Dung-Tsa Chen
  • Jonathan M. Hernandez
  • David Shibata
  • Susan M. McCarthy
  • Leigh Ann Humphries
  • Whalen Clark
  • Abul Elahi
  • Mike Gruidl
  • Domenico Coppola
  • Timothy Yeatman
2011 SSAT Plenary Presentation

Abstract

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.

Keywords

Metastates Complementary strand microRNA Colon cancer 

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Copyright information

© The Society for Surgery of the Alimentary Tract 2012

Authors and Affiliations

  • Dung-Tsa Chen
    • 2
  • Jonathan M. Hernandez
    • 1
    • 4
  • David Shibata
    • 1
  • Susan M. McCarthy
    • 1
  • Leigh Ann Humphries
    • 1
  • Whalen Clark
    • 1
    • 4
  • Abul Elahi
    • 1
  • Mike Gruidl
    • 1
  • Domenico Coppola
    • 3
  • Timothy Yeatman
    • 1
  1. 1.Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  2. 2.Department of Biomedical InformaticsH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  3. 3.Department of Anatomic PathologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  4. 4.Department of SurgeryUniversity of South FloridaTampaUSA

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