P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis

• DOI: 10.1073/pnas.0911082107
• Publication Date: 2010-03-23T02:36:27Z
• Authors: Munekazu Yamakuchi; Craig D. Lotterman; Clare Bao; Ralph H. Hruban; Baktiar Karim; Joshua T. Mendell; David Huso; Charles J. Lowens...
• Keywords: 0301 basic medicine; Base Sequence; Neovascularization, Pathologic; Transcription, Genetic; Aryl Hydrocarbon Receptor Nuclear Translocator; Mice, Nude; HCT116 Cells; Xenograft Model Antitumor Assays; Cell Hypoxia; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; MicroRNAs; 03 medical and health sciences; Neoplasms; Animals; Humans; Tumor Suppressor Protein p53; Signal Transduction

The pathway involving the tumor suppressor gene TP53 can regulate tumor angiogenesis by unclear mechanisms. Here we show that p53 regulates hypoxic signaling through the transcriptional regulation of microRNA-107 (miR-107). We found that miR-107 is a microRNA expressed by human colon cancer specimens and regulated by p53. miR-107 decreases hypoxia signaling by suppressing expression of hypoxia inducible factor-1β (HIF-1β). Knockdown of endogenous miR-107 enhances HIF-1β expression and hypoxic signaling in human colon cancer cells. Conversely, overexpression of miR-107 inhibits HIF-1β expression and hypoxic signaling. Furthermore, overexpression of miR-107 in tumor cells suppresses tumor angiogenesis, tumor growth, and tumor VEGF expression in mice. Finally, in human colon cancer specimens, expression of miR-107 is inversely associated with expression of HIF-1β. Taken together these data suggest that miR-107 can mediate p53 regulation of hypoxic signaling and tumor angiogenesis.