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 | |
| 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