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

416 Citations (Scopus)

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 - 2010

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MicroRNAs
Carcinogenesis
Lung
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Neoplasms
MAP Kinase Signaling System
Transgenic Mice
Alleles
Apoptosis
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology
  • Medicine(all)

Cite this

Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. / Hatley, Mark E.; Patrick, David M.; Garcia, Matthew R.; Richardson, James A.; Bassel-Duby, Rhonda; van Rooij, Eva; Olson, Eric N.

In: Cancer Cell, Vol. 18, No. 3, 2010, p. 282-293.

Research output: Contribution to journalArticle

Hatley, Mark E. ; Patrick, David M. ; Garcia, Matthew R. ; Richardson, James A. ; Bassel-Duby, Rhonda ; van Rooij, Eva ; Olson, Eric N. / Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. In: Cancer Cell. 2010 ; Vol. 18, No. 3. pp. 282-293.
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