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

Zehua Wang; Bo Yang; Min Zhang; Weiwei Guo; Zhiyuan Wu; Yue Wang; Lin Jia; Song Li; Wen Xie; Da Yang

doi:10.1016/j.ccell.2018.03.006

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

Zehua Wang, Bo Yang, Min Zhang, Weiwei Guo, Zhiyuan Wu, Yue Wang, Lin Jia, Song Li, Wen Xie and Da Yang

Cancer cell, Vol.33(4), pp.706-720.e9

04/09/2018

DOI: 10.1016/j.ccell.2018.03.006

PMCID: PMC6143179

PMID: 29622465

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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.

Cell Cycle

Animals

Binding Sites

Breast Neoplasms - genetics

Breast Neoplasms - pathology

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

Proto-Oncogene Proteins c-myc - genetics

RNA, Long Noncoding - chemistry

RNA, Long Noncoding - genetics

Up-Regulation

Details

Title: Subtitle: lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer
Creators: Zehua Wang - University of Pittsburgh
Bo Yang - University of Pittsburgh
Min Zhang - University of Pittsburgh
Weiwei Guo - University of Pittsburgh
Zhiyuan Wu - University of Pittsburgh
Yue Wang - University of Pittsburgh
Lin Jia - University of Pittsburgh
Song Li - University of Pittsburgh
Wen Xie - University of Pittsburgh
Da Yang - University of Pittsburgh
Contributors: Cancer Genome Atlas Research Network
Deqin Ma - University of Iowa, Pathology
Mohammed M Milhem - University of Iowa, Internal Medicine
Aaron D Bossler - University of Iowa, Pathology
Resource Type: Journal article
Publication Details: Cancer cell, Vol.33(4), pp.706-720.e9
DOI: 10.1016/j.ccell.2018.03.006
PMID: 29622465
PMCID: PMC6143179
ISSN: 1535-6108
eISSN: 1878-3686
Grant note: P50 CA159981 / NCI NIH HHS U24 CA210950 / NCI NIH HHS U24 CA210990 / NCI NIH HHS U24 CA210949 / NCI NIH HHS P30 CA047904 / NCI NIH HHS U24 CA210957 / NCI NIH HHS R01 CA163722 / NCI NIH HHS
Language: English
Date published: 04/09/2018
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
Record Identifier: 9984185168802771

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