Epigenetic dysregulation has emerged as a major contributor to tumorigenesis. Histone methylation is a well-established mechanism of epigenetic regulation that is dynamically modulated by histone methyltransferases and demethylases. The pathogenic role of histone methylation modifiers in non–small cell lung cancer (NSCLC), which is the leading cause of cancer deaths worldwide, remains largely unknown. Here, we found that the histone H3 lysine 36 (H3K36) demethylase KDM2A (also called FBXL11 and JHDM1A) is frequently overexpressed in NSCLC tumors and cell lines. KDM2A and its catalytic activity were required for in vitro proliferation and invasion of KDM2A-overexpressing NSCLC cells. KDM2A overexpression in NSCLC cells with low KDM2A levels increased cell proliferation and invasiveness. KDM2A knockdown abrogated tumor growth and invasive abilities of NSCLC cells in mouse xenograft models. We identified dual-specificity phosphatase 3 (
Klaus W. Wagner, Hunain Alam, Shilpa S. Dhar, Uma Giri, Na Li, Yongkun Wei, Dipak Giri, Tina Cascone, Jae-Hwan Kim, Yuanqing Ye, Asha S. Multani, Chia-Hsin Chan, Baruch Erez, Babita Saigal, Jimyung Chung, Hui-Kuan Lin, Xifeng Wu, Mien-Chie Hung, John V. Heymach, Min Gyu Lee
Stable knockdown of KDM2A drastically inhibits tumor growth of NSCLC cells in vivo, and high KDM2A correlates with poor prognosis of lung cancer patients.