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An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
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An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells

Published on: May 21, 2019

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

Munekazu Yamakuchi1, Craig D Lotterman, Clare Bao

  • 1Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. munekazu_yamakuchi@urmc.rochester

Proceedings of the National Academy of Sciences of the United States of America
|March 24, 2010
PubMed

Insights

The tumor suppressor p53 regulates tumor angiogenesis via microRNA-107 (miR-107). miR-107 suppresses hypoxia-inducible factor-1beta (HIF-1beta), inhibiting tumor growth and angiogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • The tumor suppressor gene TP53 plays a role in regulating tumor angiogenesis through incompletely understood mechanisms.
  • Hypoxic signaling is a critical factor in tumor development and progression.

Purpose of the Study:

  • To elucidate the mechanism by which p53 regulates tumor angiogenesis.
  • To investigate the role of microRNA-107 (miR-107) in p53-mediated regulation of hypoxic signaling and tumor angiogenesis.

Main Methods:

  • Investigated the transcriptional regulation of miR-107 by p53 in human colon cancer cells.
  • Assessed the effect of miR-107 on hypoxia-inducible factor-1beta (HIF-1beta) expression and hypoxic signaling.
  • Utilized knockdown and overexpression techniques for miR-107 in cancer cells.
  • Evaluated the impact of miR-107 overexpression on tumor growth, angiogenesis, and VEGF expression in a mouse model.
  • Correlated miR-107 and HIF-1beta expression in human colon cancer specimens.

Main Results:

  • p53 transcriptionally regulates miR-107 expression in human colon cancer.
  • miR-107 directly suppresses HIF-1beta expression, thereby decreasing hypoxic signaling.
  • Knockdown of miR-107 increases HIF-1beta and enhances hypoxic signaling in colon cancer cells.
  • Overexpression of miR-107 inhibits HIF-1beta, reduces hypoxic signaling, and suppresses tumor angiogenesis, growth, and VEGF expression in mice.
  • Human colon cancer specimens show an inverse correlation between miR-107 and HIF-1beta expression.

Conclusions:

  • miR-107 is a key mediator in the p53 pathway's regulation of hypoxic signaling.
  • miR-107 functions as a tumor suppressor by inhibiting angiogenesis and tumor growth.
  • These findings reveal a novel mechanism for p53 in controlling tumor development via the miR-107/HIF-1beta axis.

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