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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalJournal of Gastrointestinal Surgery
Volume16
Issue number5
DOIs
StatePublished - May 1 2012

Fingerprint

MicroRNAs
Adenocarcinoma
Colonic Neoplasms
Down-Regulation
Colorectal Neoplasms
Neoplasms
Carcinogenesis

All Science Journal Classification (ASJC) codes

  • Surgery
  • Gastroenterology

Cite this

Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma. / Chen, Dung Tsa; Hernandez, Jonathan M.; Shibata, David; Mccarthy, Susan M.; Humphries, Leigh Ann; Clark, Whalen; Elahi, Abul; Gruidl, Mike; Coppola, Domenico; Yeatman, Timothy.

In: Journal of Gastrointestinal Surgery, Vol. 16, No. 5, 01.05.2012, p. 905-913.

Research output: Contribution to journalArticle

Chen, DT, Hernandez, JM, Shibata, D, Mccarthy, SM, Humphries, LA, Clark, W, Elahi, A, Gruidl, M, Coppola, D & Yeatman, T 2012, 'Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma', Journal of Gastrointestinal Surgery, vol. 16, no. 5, pp. 905-913. https://doi.org/10.1007/s11605-011-1815-0
Chen, Dung Tsa ; Hernandez, Jonathan M. ; Shibata, David ; Mccarthy, Susan M. ; Humphries, Leigh Ann ; Clark, Whalen ; Elahi, Abul ; Gruidl, Mike ; Coppola, Domenico ; Yeatman, Timothy. / Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma. In: Journal of Gastrointestinal Surgery. 2012 ; Vol. 16, No. 5. pp. 905-913.
@article{161b1e5a37c24960a32e56d53cc03f3c,
title = "Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma",
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.",
author = "Chen, {Dung Tsa} and Hernandez, {Jonathan M.} and David Shibata and Mccarthy, {Susan M.} and Humphries, {Leigh Ann} and Whalen Clark and Abul Elahi and Mike Gruidl and Domenico Coppola and Timothy Yeatman",
year = "2012",
month = "5",
day = "1",
doi = "10.1007/s11605-011-1815-0",
language = "English (US)",
volume = "16",
pages = "905--913",
journal = "Journal of Gastrointestinal Surgery",
issn = "1091-255X",
publisher = "Springer New York",
number = "5",

}

TY - JOUR

T1 - Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma

AU - Chen, Dung Tsa

AU - Hernandez, Jonathan M.

AU - Shibata, David

AU - Mccarthy, Susan M.

AU - Humphries, Leigh Ann

AU - Clark, Whalen

AU - Elahi, Abul

AU - Gruidl, Mike

AU - Coppola, Domenico

AU - Yeatman, Timothy

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84865324333&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865324333&partnerID=8YFLogxK

U2 - 10.1007/s11605-011-1815-0

DO - 10.1007/s11605-011-1815-0

M3 - Article

VL - 16

SP - 905

EP - 913

JO - Journal of Gastrointestinal Surgery

JF - Journal of Gastrointestinal Surgery

SN - 1091-255X

IS - 5

ER -