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

Authors

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
Samantha J. Caesar-Johnson
John A. Demchok
Ina Felau
Melpomeni Kasapi
Martin L. Ferguson
Carolyn M. Hutter
Heidi J. Sofia
Roy Tarnuzzer
Zhining Wang
Liming Yang
Jean C. Zenklusen
Jiashan (Julia) Zhang
Sudha Chudamani
Jia Liu
Laxmi Lolla
Rashi Naresh
Todd Pihl
Qiang Sun
Yunhu Wan
Ye Wu
Juok Cho
Timothy DeFreitas
Scott Frazer
Nils Gehlenborg
Gad Getz

Document Type

Journal Article

Publication Date

4-9-2018

Journal

Cancer Cell

Volume

33

Issue

4

DOI

10.1016/j.ccell.2018.03.006

Keywords

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

Abstract

© 2018 Elsevier Inc. 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. Wang et al. characterize the epigenetic landscape of lncRNAs genes across a large number of human tumors and cancer cell lines and observe recurrent hypomethylation of lncRNA genes, including EPIC1. EPIC1 RNA promotes cell-cycle progression by interacting with MYC and enhancing its binding to target genes.

APA Citation

Wang, Z., Yang, B., Zhang, M., Guo, W., Wu, Z., Wang, Y., Jia, L., Li, S., Caesar-Johnson, S., Demchok, J., Felau, I., Kasapi, M., Ferguson, M., Hutter, C., Sofia, H., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J., Zhang, J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., & Getz, G. (2018). lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer. Cancer Cell, 33 (4). http://dx.doi.org/10.1016/j.ccell.2018.03.006