High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells
High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells
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DOI：
10.3748/wjg.15.2089
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发表时间：
2009-05-07
影响因子：
4.3
通讯作者：
Gockel, Ines
中科院分区：
文献类型：
--
作者：
Schimanski, Carl Christoph;Frerichs, Kirsten;Gockel, Ines
目的：分析miR-196A与结直肠癌发生发展的相关性。方法：用逆转录聚合酶链式反应(RT-PCR)检测瞬时转染SW480癌细胞后miR-196A对限制靶基因HoxA7、HoxB8、HoxC8和HoxD8的影响。用RT-PCR方法对结直肠癌标本、粘膜标本和不同癌细胞系中miR-196A的转录水平进行定量。结果：miR-196A对HoxA7、HoxB8、HoxC8和HoxD8具有剂量依赖性和基因特异性的抑制作用。高水平的miR-196A激活了AKT信号通路，这表明AKT的磷酸化增加。此外，高水平的miR-196A促进癌细胞对铂类化合物的分离、迁移、侵袭和化疗敏感性，但不影响增殖或凋亡。结论：miR-196A在结直肠癌中具有促肿瘤作用。(C)2009年WIG Press和白石登。版权所有。
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.(C) 2009 The WIG Press and Baishideng. All rights reserved.