MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels
Abstract
The MYC oncogene broadly promotes transcription mediated by all nuclear RNA polymerases, thereby acting as a positive modifier of global gene expression. Here, we report that MYC stimulates the transcription of DANCR, a long noncoding RNA (lncRNA) that is widely overexpressed in human cancer. We identified DANCR through its overexpression in a transgenic model of MYC-induced lymphoma, but found that it was broadly upregulated in many human cancer cell lines and cancers, including most notably in prostate and ovarian cancers. Mechanistic investigations indicated that DANCR limited the expression of cell-cycle inhibitor p21 (CDKN1A) and that the inhibitory effects of DANCR loss on cell proliferation could be partially rescued by p21 silencing. In a xenograft model of human ovarian cancer, a nanoparticle-mediated siRNA strategy to target DANCR in vivo was sufficient to strongly inhibit tumor growth. Our observations expand knowledge of how MYC drives cancer cell proliferation by identifying DANCR as a critical lncRNA widely overexpressed in human cancers.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2018
- Source ID
- 10.1158/0008-5472.can-17-0815
Entities
People
- Angelo M. Demarzo
- Anil K. Sood
- Chi V. Dang
- Cristian Rodriguez-Aguayo
- Dahai Jiang
- Gabriel Lopez-berestein
- Lin Zhang
- Lingegowda S. Mangala
- Sunila Pradeep
- Xiaowen Hu
- Yan Xiang
- Youyou Zhang
- Yunqi Lu
- Zachary E. Stine
- Zhongyi Hu
Organizations
- Johns Hopkins University
- National Cancer Institute
- United States Department of Defense
- University of Pennsylvania
- University of Texas at Austin