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

Published

Journal Article

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 14 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 gynecologic cancer cells. Our analysis indicates that, although 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.

Full Text

Duke Authors

Cited Authors

  • Chiu, H-S; Somvanshi, S; Patel, E; Chen, T-W; Singh, VP; Zorman, B; Patil, SL; Pan, Y; Chatterjee, SS; Cancer Genome Atlas Research Network, ; Sood, AK; Gunaratne, PH; Sumazin, P

Published Date

  • April 3, 2018

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 297 - 312.e12

PubMed ID

  • 29617668

Pubmed Central ID

  • 29617668

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2018.03.064

Language

  • eng

Conference Location

  • United States