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

Z. Wang, B. Yang, M. Zhang, W. Guo, Z. Wu, Y. Wang, L. Jia, S. Li, Cancer Genome Atlas Research Network, W. Xie, D. Yang, M. (come contributors) Marino

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)706-720.e9
JournalCancer Cell
Volume33
Issue number4
DOIs
Publication statusPublished - Apr 9 2018
Externally publishedYes

Fingerprint

Long Noncoding RNA
Epigenomics
Cell Cycle
Neoplasms
Breast Neoplasms
CpG Islands
Neoplasm Genes
Genes
Carcinogenesis
Phenotype
Cell Line
Growth
In Vitro Techniques

Keywords

  • CIMP
  • ENSG00000224271
  • EPIC1
  • LOC284930
  • MYC
  • P21
  • TCGA pan-cancer
  • breast cancer
  • long noncoding RNA

Cite this

lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer. / Wang, Z.; Yang, B.; Zhang, M.; Guo, W.; Wu, Z.; Wang, Y.; Jia, L.; Li, S.; Network, Cancer Genome Atlas Research; Xie, W.; Yang, D.; Marino, M. (come contributors).

In: Cancer Cell, Vol. 33, No. 4, 09.04.2018, p. 706-720.e9.

Research output: Contribution to journalArticle

Wang, Z, Yang, B, Zhang, M, Guo, W, Wu, Z, Wang, Y, Jia, L, Li, S, Network, CGAR, Xie, W, Yang, D & Marino, MC 2018, 'lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer', Cancer Cell, vol. 33, no. 4, pp. 706-720.e9. https://doi.org/10.1016/j.ccell.2018.03.006
Wang, Z. ; Yang, B. ; Zhang, M. ; Guo, W. ; Wu, Z. ; Wang, Y. ; Jia, L. ; Li, S. ; Network, Cancer Genome Atlas Research ; Xie, W. ; Yang, D. ; Marino, M. (come contributors). / lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer. In: Cancer Cell. 2018 ; Vol. 33, No. 4. pp. 706-720.e9.
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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.",
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