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MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels. Cancer Res 2018 01 01;78(1):64-74

Date

11/29/2017

Pubmed ID

29180471

Pubmed Central ID

PMC5993051

DOI

10.1158/0008-5472.CAN-17-0815

Scopus ID

2-s2.0-85040179207   51 Citations

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.

Author List

Lu Y, Hu Z, Mangala LS, Stine ZE, Hu X, Jiang D, Xiang Y, Zhang Y, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, DeMarzo AM, Sood AK, Zhang L, Dang CV

Author

Sunila Pradeep PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21
Female
Gene Expression Regulation, Neoplastic
Genes, myc
Humans
Lymphoma, B-Cell
Male
Mice, Nude
Ovarian Neoplasms
Prostatic Neoplasms
RNA, Long Noncoding
Xenograft Model Antitumor Assays
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a