Author:
Zeitels Lauren R.,Acharya Asha,Shi Guanglu,Chivukula Divya,Chivukula Raghu R.,Anandam Joselin L.,Abdelnaby Abier A.,Balch Glen C.,Mansour John C.,Yopp Adam C.,Richardson James A.,Mendell Joshua T.
Abstract
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 Apcmin/+ 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.
Funder
Cancer Prevention Research Institute of Texas
National Institutes of Health
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
56 articles.
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