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lncRNA epigenetic landscape analysis identifies EPIC1 as an oncogenic lncRNA that interacts with MYC and promotes cell-cycle progression in cancer

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Title: lncRNA epigenetic landscape analysis identifies EPIC1 as an oncogenic lncRNA that interacts with MYC and promotes cell-cycle progression in cancer
Authors: Wang, Z
Yang, B
Zhang, M
Guo, W
Wu, Z
Wang, Y
Jia, L
Li, S
Xie, W
Yang, D
Item Type: Journal Article
Abstract: We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to the CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation of 1,006 lncRNA genes in cancer, including EPIC1 (epigenetically-induced lncRNA1). Overexpression of EPIC1 is associated with poor prognosis in luminal B breast cancer patients and enhances tumor growth in vitro and in vivo. Mechanistically, EPIC1 promotes cell-cycle progression by interacting with MYC through EPIC1's 129–283 nt region. EPIC1 knockdown reduces the occupancy of MYC to its target genes (e.g., CDKN1A, CCNA2, CDC20, and CDC45). MYC depletion abolishes EPIC1's regulation of MYC target and luminal breast cancer tumorigenesis in vitro and in vivo.
Issue Date: 9-Apr-2018
Date of Acceptance: 5-Mar-2018
URI: http://hdl.handle.net/10044/1/71238
DOI: https://doi.org/10.1016/j.ccell.2018.03.006
ISSN: 1535-6108
Publisher: Elsevier
Start Page: 706
End Page: 720.e9
Journal / Book Title: Cancer Cell
Volume: 33
Issue: 4
Copyright Statement: © 2018 Elsevier Inc. 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
Oncology
Cell Biology
LONG NONCODING RNA
C-MYC
TRANSCRIPTIONAL NETWORK
GENE-EXPRESSION
ANALYSES REVEAL
BINDING-SITES
GENOME
PROTEIN
METHYLATION
SEQ
CIMP
ENSG00000224271
EPIC1
LOC284930
MYC
P21
TCGA pan-cancer
breast cancer
long noncoding RNA
Animals
Binding Sites
Breast Neoplasms
Cell Cycle
Cell Line, Tumor
CpG Islands
DNA Methylation
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Neoplasm Transplantation
Prognosis
Promoter Regions, Genetic
Proto-Oncogene Proteins c-myc
RNA, Long Noncoding
Up-Regulation
Cancer Genome Atlas Research Network
Cell Line, Tumor
Animals
Humans
Mice
Breast Neoplasms
Proto-Oncogene Proteins c-myc
Prognosis
Neoplasm Transplantation
Cell Cycle
DNA Methylation
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Up-Regulation
Binding Sites
CpG Islands
Female
Promoter Regions, Genetic
RNA, Long Noncoding
Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
LONG NONCODING RNA
C-MYC
TRANSCRIPTIONAL NETWORK
GENE-EXPRESSION
ANALYSES REVEAL
BINDING-SITES
GENOME
PROTEIN
METHYLATION
SEQ
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
1109 Neurosciences
Publication Status: Published
Open Access location: https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30110-7
Online Publication Date: 2018-04-02
Appears in Collections:Department of Surgery and Cancer