Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal tumorigenesis
- Lauren R. Zeitels1,2,
- Asha Acharya2,
- Guanglu Shi2,
- Divya Chivukula2,
- Raghu R. Chivukula3,
- Joselin L. Anandam4,
- Abier A. Abdelnaby4,
- Glen C. Balch4,
- John C. Mansour4,
- Adam C. Yopp4,
- James A. Richardson2,5 and
- Joshua T. Mendell2,6,7
- 1Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 2Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
- 3Department of Medicine, The Massachusetts General Hospital, Boston, Massachusetts 02115, USA;
- 4Department of Surgery,
- 5Department of Pathology,
- 6Simmons Cancer Center,
- 7Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
- Correspondence: joshua.mendell{at}utsouthwestern.edu
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.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.250951.114.
- Received August 13, 2014.
- Accepted October 27, 2014.
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