Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal tumorigenesis

LR Zeitels, A Acharya, G Shi, D Chivukula… - Genes & …, 2014 - genesdev.cshlp.org
LR Zeitels, A Acharya, G Shi, D Chivukula, RR Chivukula, JL Anandam, AA Abdelnaby…
Genes & development, 2014genesdev.cshlp.org
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 …
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.
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