Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

摘要: Summary Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful known to play pathophysiological roles cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, microRNAs 5,185 TCGA tumors 1,019 ENCODE assays. Our predictions included hundreds candidate onco- tumor-suppressor lncRNAs) whose somatic alterations account for dysregulation dozens genes pathways each 14 contexts. To demonstrate proof concept, we showed perturbations targeting OIP5-AS1 (an suppressor) TUG1 WT1-AS (inferred onco-lncRNAs) altered proliferation breast gynecologic cells. analysis indicates that, although most tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, TSIX, synergistically multiple