title: The let-7 microRNA reduces tumor growth in mouse models of lung cancer.
abstract: MicroRNAs have been increasingly implicated in human cancer and interest has grown about the potential to use microRNAs to combat cancer. Lung cancer is the most prevalent form of cancer worldwide and lacks effective therapies. Here we have used both in vitro and in vivo approaches to show that the let-7 microRNA directly represses cancer growth in the lung. We find that let-7 inhibits the growth of multiple human lung cancer cell lines in culture, as well as the growth of lung cancer cell xenografts in immunodeficient mice. Using an established orthotopic mouse lung cancer model, we show that intranasal let-7 administration reduces tumor formation in vivo in the lungs of animals expressing a G12D activating mutation for the K-ras oncogene. These findings provide direct evidence that let-7 acts as a tumor suppressor gene in the lung and indicate that this miRNA may be useful as a novel therapeutic agent in lung cancer.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Aurora
authors.initials: A
authors.lastname: Esquela-Kerscher
authors.forename: Phong
authors.initials: P
authors.lastname: Trang
authors.forename: Jason F
authors.initials: JF
authors.lastname: Wiggins
authors.forename: Lubna
authors.initials: L
authors.lastname: Patrawala
authors.forename: Angie
authors.initials: A
authors.lastname: Cheng
authors.forename: Lance
authors.initials: L
authors.lastname: Ford
authors.forename: Joanne B
authors.initials: JB
authors.lastname: Weidhaas
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Bader
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Slack
mesh_terms: D000256:Adenoviridae; D000281:Administration, Intranasal; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D035683:MicroRNAs; C487931:mirnlet7 microRNA, human