Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis

Rajnish A. Gupta, Nilay Shah, Kevin C. Wang, Jeewon Kim, Hugo M. Horlings, David J. Wong, Miao-Chih Tsai, Tiffany Hung, Pedram Argani, John L. Rinn, Yulei Wang, Pius Brzoska, Benjamin Kong, Rui Li, Robert B. West, Marc J. van de Vijver, Saraswati Sukumar and Howard Y. Chang ()
Additional contact information
Rajnish A. Gupta: Howard Hughes Medical Institute and Program in Epithelial Biology,
Nilay Shah: Sidney Kimmel Comprehensive Cancer Center,
Kevin C. Wang: Howard Hughes Medical Institute and Program in Epithelial Biology,
Jeewon Kim: Stanford Cancer Center and Transgenic Mouse Research Center,
Hugo M. Horlings: Academic Medical Center, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands
David J. Wong: Howard Hughes Medical Institute and Program in Epithelial Biology,
Miao-Chih Tsai: Howard Hughes Medical Institute and Program in Epithelial Biology,
Tiffany Hung: Howard Hughes Medical Institute and Program in Epithelial Biology,
Pedram Argani: Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
John L. Rinn: The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
Yulei Wang: Applied Biosystems, Foster City, California 94404, USA
Pius Brzoska: Applied Biosystems, Foster City, California 94404, USA
Benjamin Kong: Applied Biosystems, Foster City, California 94404, USA
Rui Li: Stanford University School of Medicine, Stanford, California 94305, USA
Robert B. West: Stanford University School of Medicine, Stanford, California 94305, USA
Marc J. van de Vijver: Academic Medical Center, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands
Saraswati Sukumar: Sidney Kimmel Comprehensive Cancer Center,
Howard Y. Chang: Howard Hughes Medical Institute and Program in Epithelial Biology,

Nature, 2010, vol. 464, issue 7291, 1071-1076

Abstract: Chromatin in cancer metastasis Long non-coding RNAs (lincRNAs), a relatively recently recognized class of widely transcribed genes, are thought to affect chromatin state and epigenetic regulation, but their mechanisms of action and potential roles in human disease are poorly understood. This study shows that long non-coding RNAs in the human HOX loci are systematically dysregulated during breast cancer progression, and that expression levels of the lincRNA termed HOTAIR can predict cancer metastasis. Elevated levels of HOTAIR can lead to altered patterns of Polycomb binding to the genome. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.

Date: 2010
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DOI: 10.1038/nature08975

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