High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells.
OBJECTIVE
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.


CONCLUSIONS
miR-196a exerts a pro-oncogenic influence in colorectal cancer.
First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. dr_schimanski@yahoo.de
Carl Christoph
CC
Schimanski
Kirsten
K
Frerichs
Fareed
F
Rahman
Martin
M
Berger
Hauke
H
Lang
Peter R
PR
Galle
Markus
M
Moehler
Ines
I
Gockel
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003106:Colon / Q000033:anatomy & histology / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous
C542543:MIRN196 microRNA, human; D035683:MicroRNAs