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Cancer Research 67, 7713, August 15, 2007. doi: 10.1158/0008-5472.CAN-07-1083
© 2007 American Association for Cancer Research
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Cell, Tumor, and Stem Cell Biology

The let-7 MicroRNA Represses Cell Proliferation Pathways in Human Cells

Charles D. Johnson1, Aurora Esquela-Kerscher3, Giovanni Stefani3, Mike Byrom1, Kevin Kelnar1, Dmitriy Ovcharenko1, Mike Wilson1, Xiaowei Wang2, Jeffrey Shelton1, Jaclyn Shingara1, Lena Chin3, David Brown1 and Frank J. Slack3

1 Asuragen, Inc.; 2 Ambion, Inc., Austin, Texas, and 3 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut

Requests for reprints: Frank J. Slack, Department of Molecular, Cellular and Developmental Biology, P.O. Box 208103, Yale University, New Haven, CT 06520. Phone: 203-432-3492; Fax: 203-432-6161; E-mail: frank.slack{at}yale.edu or David Brown, Asuragen, Inc., 2150 Woodward St., Austin, TX 78744. E-mail: dbrown{at}asuragen.com.

MicroRNAs play important roles in animal development, cell differentiation, and metabolism and have been implicated in human cancer. The let-7 microRNA controls the timing of cell cycle exit and terminal differentiation in Caenorhabditis elegans and is poorly expressed or deleted in human lung tumors. Here, we show that let-7 is highly expressed in normal lung tissue, and that inhibiting let-7 function leads to increased cell division in A549 lung cancer cells. Overexpression of let-7 in cancer cell lines alters cell cycle progression and reduces cell division, providing evidence that let-7 functions as a tumor suppressor in lung cells. let-7 was previously shown to regulate the expression of the RAS lung cancer oncogenes, and our work now shows that multiple genes involved in cell cycle and cell division functions are also directly or indirectly repressed by let-7. This work reveals the let-7 microRNA to be a master regulator of cell proliferation pathways. [Cancer Res 2007;67(16):7713–22]




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2007 by the American Association for Cancer Research.