Cell Reports. Volume 23, Issue 1 p297-312.e12, 3 April 2018 10.1016/j.celrep.2018.03.064
Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors but only a handful are known to play pathophysiological roles in 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, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of fourteen tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1—an inferred tumor suppressor—and TUG1 and WT1 AS—inferred onco-lncRNAs—dysregulated cancer genes and altered proliferation of breast and gynecological cancer cells. Our analysis indicates that while most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts.
Data in the GDC
- GDC Manifests
- Open-Access Data - Download Manifest (6 Files)
Supplemental Data
- Data Files
- List of lncRNAs and canonical regulators - LongHorn-Data1.zip
- List of proximal promoters of protein-coding targets - LongHorn-Data2.zip
- List of 3prime UTRs of protein-coding targets - LongHorn-Data3.zip
- LongHorn-inferred targets of lncRNAs in PAN14 - LongHorn-Data4.zip
- LongHorn-inferred targets of canonical regulators in PAN14 - LongHorn-Data5.zip
- Hallmark gene set enrichment analysis in PAN14 - LongHorn-Data6.zip
Additional Resources
- Broad Institute FireCloud (link is external) The Broad Institute
- cBioPortal for Cancer Genomics (link is external) Memorial Sloan-Kettering Cancer Center
- PanCanAtlas Additional Files
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