MYC targeted long noncoding RNA DANCR promotes cancer in part by reducing p21 levels

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)64-74
Number of pages11
JournalCancer Research
Volume78
Issue number1
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Lu, Y., Hu, Z., Mangala, L. S., Stine, Z. E., Hu, X., Jiang, D., Xiang, Y., Zhang, Y., Pradeep, S., Rodriguez-Aguayo, C., Lopez-Berestein, G., DeMarzo, A. M., Sood, A. K., Zhang, L., & Dang, C. V. (2018). MYC targeted long noncoding RNA DANCR promotes cancer in part by reducing p21 levels. Cancer Research, 78(1), 64-74. https://doi.org/10.1158/0008-5472.CAN-17-0815