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
CANCER CELL | CELL PRESS | Published : 2018
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 ..View full abstract
Awarded by Career Development Award of RPCI-UPCI Ovarian Cancer SPORE
Awarded by NATIONAL CANCER INSTITUTE
This study was supported by a grant from the Shear Family Foundation (to D.Y.), a Career Development Award of RPCI-UPCI Ovarian Cancer SPORE (P50 CA159981; to D.Y.), and a grant from the Elsa U. Pardee Foundation (to D.Y.). This project is supported in part by award P30CA047904. We thank The Center for Simulation and Modeling (SaM) at the University of Pittsburgh for computing assistance. We thank The Center for Biologic Imaging (CBI) at the University of Pittsburgh for imaging assistance. We thank Drs. Nara Lee, Barry Gold, Anil Sood, Wei Zhang, and Ilya Shmulevich for internal critical review.