p54/nrb对前列腺癌中PCGEM1的调控
Regulation of PCGEM1 by p54/nrb in prostate cancer.
作者信息
Ho Tsui-Ting, Huang Jianguo, Zhou Nanjiang, Zhang Ziqiang, Koirala Pratirodh, Zhou Xinchun, Wu Fangting, Ding Xianfeng, Mo Yin-Yuan
机构信息
Department of Pharmacology and Toxicology, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA.
出版信息
Sci Rep. 2016 Sep 29;6:34529. doi: 10.1038/srep34529.
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.
PCGEM1是一种长链非编码RNA（lncRNA），在前列腺癌中常常上调。然而，关于PCGEM1如何被调控却知之甚少。在本研究中，我们展示了p54/nrb对雄激素剥夺响应时PCGEM1的转录调控。虽然p54/nrb的异位表达增加，但RNA干扰（RNAi）或基因敲除（KO）对p54/nrb的抑制会降低PCGEM1。此外，拯救实验表明，在KO细胞中重新表达p54/nrb可恢复诱导PCGEM1的能力，导致雄激素受体剪接变体AR3上调，而AR3已被证明在去势抵抗中起作用。最后，3,3'-二吲哚甲烷（DIM）是一种已知的化学预防剂，它能够通过阻止p54/nrb与PCGEM1启动子的相互作用来抑制PCGEM1的表达。特别是，在去势异种移植小鼠模型中，DIM通过抑制PCGEM1和促进细胞凋亡来减少肿瘤生长。总之，这些结果证明了p54/nrb介导PCGEM1和AR3表达的新机制，这与前列腺癌的去势抵抗有关。
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