Regulation of PCGEM1 by p54/nrb in prostate cancer.
Regulation of PCGEM1 by p54/nrb in prostate cancer.
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DOI：
10.1038/srep34529
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发表时间：
2016-09-29
影响因子：
4.6
通讯作者：
Mo YY
中科院分区：
文献类型：
--
作者：
Ho TT;Huang J;Zhou N;Zhang Z;Koirala P;Zhou X;Wu F;Ding X;Mo YY
PCGEM 1是一种长链非编码RNA（lncRNA），通常在前列腺癌中上调。然而，很少有人知道PCGEM 1是如何调节的。在本研究中，我们显示了PCGEM 1的转录调控响应雄激素剥夺的p54/nrb。虽然p54/nrb的异位表达增加，但通过RNAi或敲除（KO）抑制p54/nrb可减少PCGEM 1。此外，拯救实验表明，KO细胞中p54/nrb的再表达恢复了诱导PCGEM 1的能力，导致雄激素受体剪接变体AR 3的上调，AR 3已被证明在去势抵抗中起作用。最后，已知的化学预防剂3，3 ′-二吲哚基甲烷（DIM）能够通过阻止p54/nrb与PCGEM 1启动子的相互作用来抑制PCGEM 1表达。特别是，DIM通过抑制PCGEM 1和促进去势异种移植小鼠模型中的细胞凋亡来减少肿瘤生长。总之，这些结果证明了p54/nrb介导的PCGEM 1和AR 3表达的新机制，有助于前列腺癌的去势抵抗。
PCGEM1 is a long non-coding RNA (lncRNA) that is often upregulated in prostate cancer. However, little is known how PCGEM1 is regulated. In the present study, we show transcriptional regulation of PCGEM1 in response to androgen deprivation by p54/nrb. While ectopic expression of p54/nrb increases, suppression of p54/nrb by RNAi or knockout (KO) reduces PCGEM1. Moreover, rescue experiments indicate that re-expression of p54/nrb in KO cells restores the ability to induce PCGEM1, leading to upregulation of the androgen receptor splice variant AR3 which has been shown to play a role in castration resistance. Finally, 3,3′-Diindolylmethane (DIM), a known chemoprevention agent, is capable of suppressing PCGEM1 expression by preventing the interaction of p54/nrb with the PCGEM1 promoter. In particular, DIM reduces tumor growth by suppression of PCGEM1 and promoting apoptosis in the castrated xenograft mouse model. Together, these results demonstrate a novel mechanism of p54/nrb-mediated expression of PCGEM1 and AR3, contributing to castration resistance in prostate cancer.
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影响因子：
8
作者：
Petrovics, G;Zhang, W;Srivastava, S
通讯作者：
Srivastava, S
影响因子：
64.8
作者：
Konermann S;Brigham MD;Trevino AE;Joung J;Abudayyeh OO;Barcena C;Hsu PD;Habib N;Gootenberg JS;Nishimasu H;Nureki O;Zhang F
通讯作者：
Zhang F
影响因子：
14.9
作者：
Ho TT;Zhou N;Huang J;Koirala P;Xu M;Fung R;Wu F;Mo YY
通讯作者：
Mo YY
DOI：
10.1056/nejmoa1315815
发表时间：
2014-09-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Antonarakis ES;Lu C;Wang H;Luber B;Nakazawa M;Roeser JC;Chen Y;Mohammad TA;Chen Y;Fedor HL;Lotan TL;Zheng Q;De Marzo AM;Isaacs JT;Isaacs WB;Nadal R;Paller CJ;Denmeade SR;Carducci MA;Eisenberger MA;Luo J
通讯作者：
Luo J
影响因子：
50.3
作者：
Calin, George A.;Liu, Chang-Gong;Croce, Carlo M.
通讯作者：
Croce, Carlo M.