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Genes Dev ; 28(23): 2585-90, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25395662

RESUMO

Down-regulation of miR-26 family members has been implicated in the pathogenesis of multiple malignancies. In some settings, including glioma, however, miR-26-mediated repression of PTEN promotes tumorigenesis. To investigate the contexts in which the tumor suppressor versus oncogenic activity of miR-26 predominates in vivo, we generated miR-26a transgenic mice. Despite measureable repression of Pten, elevated miR-26a levels were not associated with malignancy in transgenic animals. We documented reduced miR-26 expression in human colorectal cancer and, accordingly, showed that miR-26a expression potently suppressed intestinal adenoma formation in Apc(min/+) mice, a model known to be sensitive to Pten dosage. These studies reveal a tumor suppressor role for miR-26 in intestinal cancer that overrides putative oncogenic activity, highlighting the therapeutic potential of miR-26 delivery to this tumor type.


Assuntos
Adenoma/fisiopatologia , Carcinogênese/genética , Neoplasias Intestinais/fisiopatologia , MicroRNAs/metabolismo , Adenoma/genética , Animais , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/fisiopatologia , Neoplasias Intestinais/genética , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , Células Tumorais Cultivadas
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