TY - JOUR
T1 - Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
AU - The Cancer Genome Atlas Research Network
AU - Chiu, Hua Sheng
AU - Somvanshi, Sonal
AU - Patel, Ektaben
AU - Chen, Ting Wen
AU - Singh, Vivek P.
AU - Zorman, Barry
AU - Liu, Yuexin
AU - Zhang, Wei
AU - Akbani, Rehan
AU - Broom, Bradley M.
AU - Ju, Zhenlin
AU - Kanchi, Rupa S.
AU - Korkut, Anil
AU - Li, Jun
AU - Liang, Han
AU - Ling, Shiyun
AU - Liu, Wenbin
AU - Lu, Yiling
AU - Mills, Gordon B.
AU - Rao, Arvind
AU - Weinstein, John N.
AU - Zhang, Jiexin
AU - Liu, Xiuping
AU - Wang, Linghua
AU - Carvalho, Andre L.
AU - Fregnani, José H.
AU - Reis, Rui M.
AU - Scapulatempo-Neto, Cristovam
AU - Ajani, Jaffer A.
AU - Behrens, Carmen
AU - Bondaruk, Jolanta
AU - Broaddus, Russell
AU - Czerniak, Bogdan
AU - Esmaeli, Bita
AU - Fujimoto, Junya
AU - Gershenwald, Jeffrey
AU - Guo, Charles
AU - Lazar, Alexander J.
AU - Logothetis, Christopher
AU - Meric-Bernstam, Funda
AU - Moran, Cesar
AU - Ramondetta, Lois
AU - Rice, David
AU - Tamboli, Pheroze
AU - Thompson, Timothy
AU - Troncoso, Patricia
AU - Tsao, Anne
AU - Wistuba, Ignacio
AU - von Deimling, Andreas
AU - Sood, Anil K.
N1 - Publisher Copyright:
© 2018 The Author(s)
PY - 2018/4/3
Y1 - 2018/4/3
N2 - 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. Chiu et al. present a pan-cancer analysis of lncRNA regulatory interactions. They suggest that the dysregulation of hundreds of lncRNAs target and alter the expression of cancer genes and pathways in each tumor context. This implies that hundreds of lncRNAs can alter tumor phenotypes in each tumor context.
AB - 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. Chiu et al. present a pan-cancer analysis of lncRNA regulatory interactions. They suggest that the dysregulation of hundreds of lncRNAs target and alter the expression of cancer genes and pathways in each tumor context. This implies that hundreds of lncRNAs can alter tumor phenotypes in each tumor context.
KW - RNA-binding proteins
KW - cancer gene
KW - interactome
KW - lncRNA
KW - microRNA
KW - modulation
KW - noncoding RNA
KW - pan-cancer
KW - regulation
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UR - http://www.scopus.com/inward/citedby.url?scp=85044858983&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.03.064
DO - 10.1016/j.celrep.2018.03.064
M3 - Article
C2 - 29617668
AN - SCOPUS:85044858983
SN - 2211-1247
VL - 23
SP - 297-312.e12
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -