Schimanski Carl Christoph, Frerichs Kirsten, Rahman Fareed, Berger Martin, Lang Hauke, Galle Peter R, Moehler Markus, Gockel Ines
First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
World J Gastroenterol. 2009 May 7;15(17):2089-96. doi: 10.3748/wjg.15.2089.
To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.
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.
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.
miR-196a exerts a pro-oncogenic influence in colorectal cancer.
分析微小RNA miR-196a与结直肠癌发生的相关性。
在SW480癌细胞瞬时转染后，通过逆转录聚合酶链反应（RT-PCR）分析miR-196a对限制靶点HoxA7、HoxB8、HoxC8和HoxD8的影响。通过RT-PCR对结直肠癌样本、黏膜样本及多种癌细胞系中的miR-196a转录谱进行定量分析。将瞬时转染miR-196a的结直肠癌细胞用于体外多种功能测定及体内异种移植肺转移模型。
HoxA7、HoxB8、HoxC8和HoxD8受到miR-196a以剂量依赖性和基因特异性方式的限制。如AKT磷酸化增加所示，高水平的miR-196a激活了AKT信号通路。此外，高水平的miR-196a促进癌细胞脱离、迁移、侵袭及对铂衍生物的化疗敏感性，但不影响增殖或凋亡。此外，尾静脉注射后，miR-196a增加了小鼠肺转移的发生。
miR-196a在结直肠癌中发挥促癌作用。
