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

Munekazu Yamakuchi, Craig D. Lotterman, Clare Bao, Ralph H. Hruban, Baktiar Karim, Joshua T. Mendell, David Huso, Charles J. Lowenstein

Research output: Contribution to journalArticle

303 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6334-6339
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number14
DOIs
StatePublished - Apr 6 2010

Keywords

  • Cancer
  • Endothelial
  • Hypoxia
  • Nitric oxide
  • PANK1

ASJC Scopus subject areas

  • General

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