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Priority Report

The let-7 microRNA reduces tumor growth in mouse models of lung cancer

Aurora Esquela-Kerscher, Phong Trang, Jason F. Wiggins, Lubna Patrawala, Angie Cheng, Lance Ford, Joanne B. Weidhaas, David Brown, Andreas G. Bader and Frank J. Slack

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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

Yale University; New Haven, CT

Phong Trang

Yale University; New Haven, CT

Jason F. Wiggins

Asuragen, Inc.; Austin, TX

Lubna Patrawala

Asuragen, Inc.; Austin, TX

Angie Cheng

Ambion, Inc.; Austin, TX

Lance Ford

Ambion, Inc.; Austin, TX

Joanne B. Weidhaas

Yale University School of Medicine; New Haven, CT

David Brown

Asuragen, Inc.; Austin, TX

Andreas G. Bader

Asuragen, Inc.; Austin, TX

Frank J. Slack

Yale University; New Haven, CT

Purchase article for $19

Subscribe to this journal for $129/year