Grant: Project Grant

BC200 RNA is a 200 nucleotide, primate-specific, long non-coding RNA that is produced at high levels in invasive carcinomas, whereas in normal tissue or benign tumors BC200 is not detectable at significant levels. Remarkably, studies of BC200 knockdown by our group and others demonstrate tumour-cell specific suppression of cell growth. We therefore propose to demonstrate the role that BC200 plays in tumour cell proliferation/migration and investigate possible therapeutic approaches to disrupt BC200 function. We will investigate possible protein binding partners of BC200 using mass spectrometry approaches. Protein targets will be validated and pathways that they regulate in cancer investigated through examination of entire regulatory networks. We will also examine BC200 suppression as a novel therapeutic strategy by targeting specific regions of the RNA with nucleic acid/small molecule inhibitors. Inhibitor design will also focus on optimizing delivery by exploiting unique nucleic acid structural features. Based on solid preliminary data and the team assembled, the experiments proposed present a rational, novel and synergistic approach to determine the critical role of an upregulated RNA in cancer and propose plausible therapeutic strategies.