MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels.
Cancer Res
; 78(1): 64-74, 2018 01 01.
Article
en En
| MEDLINE
| ID: mdl-29180471
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
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Genes myc
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina
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ARN Largo no Codificante
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Año:
2018
Tipo del documento:
Article