Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21

Mark E. Hatley, David M. Patrick, Matthew R. Garcia, James A. Richardson, Rhonda Bassel-Duby, Eva van Rooij, Eric N. Olson

Research output: Contribution to journalArticle

439 Scopus citations

Abstract

Lung cancer is the leading cause of cancer-related deaths in the world, and non-small-cell lung cancer (NSCLC) accounts for 80% of cases. MicroRNA-21 (miR-21) expression is increased and predicts poor survival in NSCLC. Although miR-21 function has been studied in vitro with cancer cell lines, the role of miR-21 in tumor development in vivo is unknown. We utilize transgenic mice with loss-of-function and gain-of-function miR-21 alleles combined with a model of NSCLC to determine the role of miR-21 in lung cancer. We show that overexpression of miR-21 enhances tumorigenesis and that genetic deletion of miR-21 partially protects against tumor formation. MiR-21 drives tumorigenesis through inhibition of negative regulators of the Ras/MEK/ERK pathway and inhibition of apoptosis.

Original languageEnglish (US)
Pages (from-to)282-293
Number of pages12
JournalCancer Cell
Volume18
Issue number3
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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