2010 April 15; 464(7291): 1071–1076. doi:10.1038/nature08975 | 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, Howard Y. Chang
The study investigates the role of long noncoding RNA (lincRNA) HOTAIR in breast cancer metastasis. HOTAIR is significantly upregulated in primary breast tumors and metastases, and its expression level is a strong predictor of metastasis and patient death. Overexpression of HOTAIR in epithelial cancer cells leads to genome-wide relocalization of Polycomb Repressive Complex 2 (PRC2), altering histone H3 lysine 27 methylation and gene expression, which enhances cancer invasiveness and metastasis. Conversely, loss of HOTAIR inhibits cancer invasiveness, particularly in cells with excessive PRC2 activity. These findings suggest that lincRNAs play a crucial role in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.The study investigates the role of long noncoding RNA (lincRNA) HOTAIR in breast cancer metastasis. HOTAIR is significantly upregulated in primary breast tumors and metastases, and its expression level is a strong predictor of metastasis and patient death. Overexpression of HOTAIR in epithelial cancer cells leads to genome-wide relocalization of Polycomb Repressive Complex 2 (PRC2), altering histone H3 lysine 27 methylation and gene expression, which enhances cancer invasiveness and metastasis. Conversely, loss of HOTAIR inhibits cancer invasiveness, particularly in cells with excessive PRC2 activity. These findings suggest that lincRNAs play a crucial role in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.