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

Lauren R. Zeitels, Asha Acharya, Guanglu Shi, Divya Chivukula, Raghu R. Chivukula, Joselin L. Anandam, Abier A. Abdelnaby, Glen C. Balch, John C. Mansour, Adam C. Yopp, James A. Richardson, Joshua T. Mendell

Research output: Contribution to journalArticle

42 Scopus citations

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 ofPTENpromotes 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 ofPten, 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 Ptendosage. 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.

Original languageEnglish (US)
Pages (from-to)2585-2590
Number of pages6
JournalGenes and Development
Volume28
Issue number23
DOIs
StatePublished - Dec 1 2014

Keywords

  • Colon cancer
  • Intestine
  • miR-26
  • microRNA

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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