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

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.

SUBMITTER: Hatley ME

PROVIDER: S-EPMC2971666 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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

Hatley Mark E ME Patrick David M DM Garcia Matthew R MR Richardson James A JA Bassel-Duby Rhonda R van Rooij Eva E Olson Eric N EN

Cancer cell 20100901 3

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- ...[more]

PMID: 20832755

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