Compound AC1Q3QWB Selectively Disrupts HOTAIR-Mediated Recruitment of PRC2 and Enhances Cancer Therapy of DZNep
Yansheng Li, Yu Ren, Yunfei Wang, Yanli Tan, Qixue Wang, Jinquan Cai, Junhu Zhou, Chao Yang, Kai Zhao, Kaikai Yi, Weili Jin, Lin Wang, Mingyang Liu, Jingxuan Yang, Min Li, Chunsheng Kang
Over 20% of cancer 'driver' genes encode chromatin regulators. Long noncoding RNAs (lincRNAs), which are dysregulated in various cancers, play a critical role in chromatin dynamics and gene regulation by interacting with key epigenetic regulators. It has been previously reported that the lincRNA HOTAIR mediates recruitment of polycomb repressive complex 2 (PRC2) leading to aberrant transcriptional silencing of tumor suppressor genes in glioma and breast cancer. Thus, lincRNA HOTAIR can serve as a promising therapeutic target. Herein, we identified a small-molecule compound AC1Q3QWB (AQB) as a selective and efficient disruptor of HOTAIR-EZH2 interaction, resulting in blocking of PRC2 recruitment and increasing tumor suppressors expression.