title: 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.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA
authors.forename: Mark E
authors.initials: ME
authors.lastname: Hatley
authors.forename: David M
authors.initials: DM
authors.lastname: Patrick
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Garcia
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.forename: Eva
authors.initials: E
authors.lastname: van Rooij
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs