Schimanski CC, Frerichs K, Rahman F, Berger M, Lang H, Galle PR, Moehler M, Gockel I. High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells. World J Gastroenterol 2009; 15(17): 2089-2096 [PMID: 19418581 DOI: 10.3748/wjg.15.2089]
Corresponding Author of This Article
Carl Christoph Schimanski, First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. dr_schimanski@yahoo.de
Article-Type of This Article
Original Articles
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World J Gastroenterol. May 7, 2009; 15(17): 2089-2096 Published online May 7, 2009. doi: 10.3748/wjg.15.2089
High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells
Carl Christoph Schimanski, Kirsten Frerichs, Fareed Rahman, Martin Berger, Hauke Lang, Peter R Galle, Markus Moehler, Ines Gockel
Carl Christoph Schimanski, Kirsten Frerichs, Fareed Rahman, Peter R Galle, Markus Moehler, First Department of Internal Medicine, Johannes Gutenberg University of Mainz, 55131 Mainz, Germany
Martin Berger, Unit of Toxicology and Chemotherapy, German Cancer Research Centre, 69120 Heidelberg, Germany
Hauke Lang, Ines Gockel, Department of General and Abdominal Surgery, Johannes Gutenberg University of Mainz, 55131 Mainz, Germany
Author contributions: Schimanski CC, Frerichs K and Rahman F performed the majority of experiments; Moehler M, Gockel I and Berger M provided vital reagents and analytical tools and were also involved in editing the manuscript; Galle PR and Lang H coordinated the study in addition to providing financial support for this work; Schimanski CC designed the study and wrote the manuscript.
Correspondence to: Carl Christoph Schimanski, First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. dr_schimanski@yahoo.de
Telephone: +49-6131-177276
Fax: +49-6131-175595
Received: December 13, 2008 Revised: February 19, 2009 Accepted: February 26, 2009 Published online: May 7, 2009
Abstract
AIM: To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.
METHODS: The impact of miR-196a on the restriction targets HoxA7, HoxB8, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction (RT-PCR) after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectal cancer samples, mucosa samples and diverse cancer cell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo.
RESULTS: HoxA7, HoxB8, HoxC8 and HoxD8 were restricted by miR-196a in a dose-dependent and gene-specific manner. High levels of miR-196a activated the AKT signaling pathway as indicated by increased phosphorylation of AKT. In addition, high levels of miR-196a promoted cancer cell detachment, migration, invasion and chemosensitivity towards platin derivatives but did not impact on proliferation or apoptosis. Furthermore, miR-196a increased the development of lung metastases in mice after tail vein injection.
CONCLUSION: miR-196a exerts a pro-oncogenic influence in colorectal cancer.
