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

• Published in: Genes & development Vol. 28; no. 23; pp. 2585 - 2590
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01-12-2014
• Subjects: Adenoma - genetics; Adenoma - physiopathology; Animals; Carcinogenesis - genetics; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Intestinal Mucosa - cytology; Intestinal Mucosa - physiopathology; Intestinal Neoplasms - genetics; Intestinal Neoplasms - physiopathology; Mice; Mice, Transgenic; MicroRNAs - genetics; MicroRNAs - metabolism; Research Communication; Tumor Cells, Cultured; microRNA; intestine; colon cancer; miR-26
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.250951.114

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.