lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer

Cancer Genome Atlas Research Network

doi:10.1016/j.ccell.2018.03.006

lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer

Cancer Genome Atlas Research Network

Research output: Contribution to journal › Article › peer-review

343 Citations (Scopus)

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.

Original language	English
Pages (from-to)	706-720.e9
Journal	Cancer cell
Volume	33
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2018.03.006
Publication status	Published - 9 Apr 2018
Externally published	Yes

Keywords

Animals
Binding Sites
Breast Neoplasms/genetics
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/chemistry
RNA, Long Noncoding/chemistry
Up-Regulation

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10.1016/j.ccell.2018.03.006

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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",

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.",

keywords = "Animals, Binding Sites, Breast Neoplasms/genetics, 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/chemistry, RNA, Long Noncoding/chemistry, Up-Regulation",

author = "{Cancer Genome Atlas Research Network} and Zehua Wang and Bo Yang and Min Zhang and Weiwei Guo and Zhiyuan Wu and Yue Wang and Lin Jia and Song Li and Wen Xie and Da Yang",

year = "2018",

month = apr,

day = "9",

doi = "10.1016/j.ccell.2018.03.006",

language = "English",

volume = "33",

pages = "706--720.e9",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

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T1 - lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer

AU - Cancer Genome Atlas Research Network

AU - Wang, Zehua

AU - Yang, Bo

AU - Zhang, Min

AU - Guo, Weiwei

AU - Wu, Zhiyuan

AU - Wang, Yue

AU - Jia, Lin

AU - Li, Song

AU - Xie, Wen

AU - Yang, Da

PY - 2018/4/9

Y1 - 2018/4/9

N2 - 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.

AB - 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.

KW - Animals

KW - Binding Sites

KW - Breast Neoplasms/genetics

KW - Cell Cycle

KW - Cell Line, Tumor

KW - CpG Islands

KW - DNA Methylation

KW - Epigenesis, Genetic

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Mice

KW - Neoplasm Transplantation

KW - Prognosis

KW - Promoter Regions, Genetic

KW - Proto-Oncogene Proteins c-myc/chemistry

KW - RNA, Long Noncoding/chemistry

KW - Up-Regulation

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U2 - 10.1016/j.ccell.2018.03.006

DO - 10.1016/j.ccell.2018.03.006

M3 - Article

C2 - 29622465

SN - 1535-6108

VL - 33

SP - 706-720.e9

JO - Cancer cell

JF - Cancer cell

IS - 4

ER -

lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer

Abstract

Keywords

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