A Compound AC1Q3QWB Selectively Disrupts HOTAIR-Mediated Recruitment of PRC2 and Enhances Cancer Therapy of DZNep.

ABSTRACT: 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. Methods: Molecular docking and high-throughp

SUBMITTER: Li Y 

PROVIDER: S-EPMC6643429 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature