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Cancer Res. 2018 Jan 1;78(1):64-74. doi: 10.1158/0008-5472.CAN-17-0815. Epub 2017 Nov 27.

MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels.

Author information

1
Abramson Family Cancer Research Institute, Abramson Cancer Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
2
Center for Research on Reproduction and Women's Health, and Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
3
Department of Gynecologic Oncology, and Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, Houston, Texas.
4
Department of Experimental Therapeutics, and Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, Houston, Texas.
5
Departments of Pathology, Urology and Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland.
6
Department of Gynecologic Oncology, and Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, Houston, Texas. cdang@licr.org linzhang@pennmedicine.upenn.edu asood@mdanderson.org.
7
Center for Research on Reproduction and Women's Health, and Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. cdang@licr.org linzhang@pennmedicine.upenn.edu asood@mdanderson.org.
8
Abramson Family Cancer Research Institute, Abramson Cancer Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. cdang@licr.org linzhang@pennmedicine.upenn.edu asood@mdanderson.org.
9
Ludwig Institute for Cancer Research, New York, New York.
10
The Wistar Institute, Philadelphia, Pennsylvania.

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.

PMID:
29180471
PMCID:
PMC5993051
DOI:
10.1158/0008-5472.CAN-17-0815
[Indexed for MEDLINE]
Free PMC Article

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