Abstract LB-114: The long noncoding RNA HOTAIR promotes glioblastoma cell proliferation

摘要: Proceedings: AACR Annual Meeting 2014; April 5-9, San Diego, CA Glioblastoma (GBM) is the most common and aggressive primary brain malignancy in adults. The standard treatment consists of surgery followed by radiotherapy chemotherapy, although this only modestly affects patient survival. Partial tumor resection poor drug delivery to impede effective options. development high-throughput sequencing technology has allowed cancer research community identify hundreds genetic alterations such as amplification, deletion, mutation, changes gene expression. However, all information still needs be translated into new therapeutic approaches. These novel therapies may come from understanding long non-coding RNAs (lncRNAs). lncRNAs modulate transcription, regulate post-transcriptional RNA processing, translation, DNA methylation, chromatin architecture through local (cis) distance (trans) mechanisms. Although relatively few have been functionally characterized, fewer are reported oncogenic or suppressor properties. Recently, small signatures 6 long-noncoding with altered expression for glioblastoma these shown correlation overall survival. Using Helicos Next Generation Sequencing platform 12 GBM samples 8 controls were sequenced. Our lab identified potentially dysregulated GBM. Among there was well-known lncRNA HOTAIR, which found massively upregulated This observation correlated what observed other cancers. increased HOTAIR linked prognosis due metastatic events. Here we show that does not promote metastasis, but instead sustains ability cells proliferate. We demonstrate knockdown strongly impairs proliferation induces apoptosis vitro vivo experiments. To direct targets employed chirp technique (chromatin isolation precipitation), us explain how transcription involved proliferation/apoptosis shed light on cellular pathways regulated HOTAIR. In addition cell cycle regulation mediated find certain epigenetic enzyme inhibitors potently downregulate These exciting studies define a mechanism enzymes control via expression. Citation Format: Chiara Pastori, Clara Penas, Philipp Kapranov, Georges St.Laurent, Ming Zhang, Nagi Ayad, Claes Wahlestedt. noncoding promotes proliferation. [abstract]. In: Proceedings 105th American Association Cancer Research; 2014 Apr 5-9; CA. Philadelphia (PA): AACR; Res 2014;74(19 Suppl):Abstract nr LB-114. doi:10.1158/1538-7445.AM2014-LB-114