TY - JOUR
T1 - MYC targeted long noncoding RNA DANCR promotes cancer in part by reducing p21 levels
AU - Lu, Yunqi
AU - Hu, Zhongyi
AU - Mangala, Lingegowda S.
AU - Stine, Zachary E.
AU - Hu, Xiaowen
AU - Jiang, Dahai
AU - Xiang, Yan
AU - Zhang, Youyou
AU - Pradeep, Sunila
AU - Rodriguez-Aguayo, Cristian
AU - Lopez-Berestein, Gabriel
AU - DeMarzo, Angelo M.
AU - Sood, Anil K.
AU - Zhang, Lin
AU - Dang, Chi V.
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-17-0815
DO - 10.1158/0008-5472.CAN-17-0815
M3 - Article
C2 - 29180471
AN - SCOPUS:85040179207
SN - 0008-5472
VL - 78
SP - 64
EP - 74
JO - Cancer Research
JF - Cancer Research
IS - 1
ER -