The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation.

摘要: Bromodomain and extraterminal (BET) domain proteins have emerged as promising therapeutic targets in glioblastoma many other cancers. Small molecule inhibitors of BET bromodomain reduce expression several oncogenes required for Glioblastoma Multiforme (GBM) progression. However, the mechanism through which protein inhibition reduces GBM growth is not completely understood. Long noncoding RNAs (lncRNAs) are important epigenetic regulators with critical roles cancer initiation malignant progression, but mechanistic insight into their regulation by remains elusive. In this study, we used Helicos single sequencing to comprehensively profile lncRNAs differentially expressed GBM, identified a subset GBM-specific whose regulated proteins. Treatment cells bromdomain inhibitor I-BET151 reduced levels tumor-promoting lncRNA HOX transcript antisense RNA (HOTAIR) restored down-regulated lncRNAs. Conversely, overexpression HOTAIR conjunction treatment abrogates antiproliferative activity inhibitor. Moreover, chromatin immunoprecipitation analysis demonstrated binding Containing 4 (BRD4) promoter, suggesting that can directly regulate expression. Our data unravel previously unappreciated control tumor suggest modulation networks may, part, mediate effects currently clinical trials diseases.