Document Detail


The let-7 microRNA reduces tumor growth in mouse models of lung cancer.
MedLine Citation:
PMID:  18344688     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Aurora Esquela-Kerscher; Phong Trang; Jason F Wiggins; Lubna Patrawala; Angie Cheng; Lance Ford; Joanne B Weidhaas; David Brown; Andreas G Bader; Frank J Slack
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-03-03
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  7     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-04-21     Completed Date:  2008-09-15     Revised Date:  2008-12-05    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  759-64     Citation Subset:  IM    
Affiliation:
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae
Administration, Intranasal
Animals
Cell Line, Tumor
Cell Proliferation
Gene Therapy / methods*
Genes, Tumor Suppressor*
Genetic Vectors
Humans
Lung Neoplasms / genetics,  therapy*
Mice
MicroRNAs / administration & dosage,  therapeutic use*
Grant Support
ID/Acronym/Agency:
F32CA130376/CA/NCI NIH HHS; F32GM071157/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/MicroRNAs; 0/mirnlet7 microRNA, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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