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.Significance: These findings expand knowledge of how MYC drives cancer cell proliferation by identifying an oncogenic long noncoding RNA that is widely overexpressed in human cancers. Cancer Res; 78(1); 64-74. ©2017 AACR.

• Authors: Yunqi Lu, Zhongyi Hu, Lingegowda S Mangala, Zachary E Stine, Xiaowen Hu, Dahai Jiang, Yan Xiang, Youyou Zhang, Sunila Pradeep, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Angelo M DeMarzo, Anil K Sood, Lin Zhang, Chi V Dang
• Journal: Cancer research (Cancer Res) Vol. 78 Issue 1 Pg. 64-74 (01 01 2018) ISSN: 1538-7445 [Electronic] United States
• PMID: 29180471 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• DANCR long noncoding RNA, human
• RNA, Long Noncoding

Topics

• Animals
• Cell Line, Tumor
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Genes, myc
• Humans
• Lymphoma, B-Cell (genetics, pathology)
• Male
• Mice, Nude
• Ovarian Neoplasms (genetics, pathology)
• Prostatic Neoplasms (genetics, pathology)
• RNA, Long Noncoding (genetics)
• Xenograft Model Antitumor Assays