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Pan-cancer analysis of lncRNA regulation supports their targeting of cancer genes ineach tumor context

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Title: Pan-cancer analysis of lncRNA regulation supports their targeting of cancer genes ineach tumor context
Authors: Chiu, H-S
Somvanshi, S
Patel, E
Chen, T-W
Singh, VP
Zorman, B
Patil, SL
Pan, Y
Chatterjee, SS
Sood, AK
Gunaratne, PH
Sumazin, P
Item Type: Journal Article
Abstract: 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.
Issue Date: 3-Apr-2018
Date of Acceptance: 15-Mar-2018
URI: http://hdl.handle.net/10044/1/71247
DOI: https://doi.org/10.1016/j.celrep.2018.03.064
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 297
End Page: 312.e12
Journal / Book Title: Cell Reports
Volume: 23
Issue: 1
Copyright Statement: © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
LONG NONCODING RNAS
HUMAN TRANSCRIPTION FACTORS
SET ENRICHMENT ANALYSIS
FACTOR-BINDING SITES
COEXPRESSION NETWORK
CELL-PROLIFERATION
MICRORNA-TARGET
EXPRESSION
GENOME
LANDSCAPE
RNA-binding proteins
cancer gene
interactome
lncRNA
microRNA
modulation
noncoding RNA
pan-cancer
regulation
Cancer Genome Atlas Research Network
Science & Technology
Life Sciences & Biomedicine
Cell Biology
LONG NONCODING RNAS
HUMAN TRANSCRIPTION FACTORS
SET ENRICHMENT ANALYSIS
FACTOR-BINDING SITES
COEXPRESSION NETWORK
CELL-PROLIFERATION
MICRORNA-TARGET
EXPRESSION
GENOME
LANDSCAPE
Publication Status: Published
Open Access location: https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30425-X?_returnURL=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112471830425X%3Fshowall%3Dtrue
Online Publication Date: 2018-04-05
Appears in Collections:Department of Surgery and Cancer