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Cancer Cell. 2010 Sep 14;18(3):282-93. doi: 10.1016/j.ccr.2010.08.013.

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

Author information

1
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA

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.

PMID:
20832755
PMCID:
PMC2971666
DOI:
10.1016/j.ccr.2010.08.013
[Indexed for MEDLINE]
Free PMC Article

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