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2018 ; 23
(1
): 297-312.e12
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Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes
in Each Tumor Context
#MMPMID29617668
Chiu HS
; Somvanshi S
; Patel E
; Chen TW
; Singh VP
; Zorman B
; Patil SL
; Pan Y
; Chatterjee SS
; Sood AK
; Gunaratne PH
; Sumazin P
Cell Rep
2018[Apr]; 23
(1
): 297-312.e12
PMID29617668
show ga
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.