The chromatin remodeling protein BRG1 links ELOVL3 trans-activation to prostate cancer metastasis
The chromatin remodeling protein BRG1 links ELOVL3 trans-activation to prostate cancer metastasis
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染色质重塑蛋白 BRG1 将 ELOVL3 反式激活与前列腺癌转移联系起来
DOI：
10.1016/j.bbagrm.2019.05.005
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发表时间：
2019
影响因子：
4.7
通讯作者：
Xu Yong
中科院分区：
文献类型：
--
作者：
Yang Yuyu;Liu Li;Li Min;Cheng Xian;Fang Mingming;Zeng Qingqi;Xu Yong
前列腺癌恶性肿瘤与脂肪酸代谢失调密切相关。潜在的表观遗传机制尚未完全理解。在本研究中，我们研究了染色质重塑蛋白BRG 1调节前列腺癌细胞中长链脂肪酸延长酶3（Elovl 3）转录的机制。我们报道，在前列腺癌细胞中，BRG 1表达对促转移信号（雄激素和TGF-β）的响应与Elvol 3一起沿着上调。BRG 1过表达增强，而BRG 1敲低减弱前列腺癌细胞的迁移和侵袭。巧合的是，在前列腺癌细胞中，Elovl 3在BRG 1过表达后上调，而在BRG 1敲低后下调。进一步的分析显示，BRG 1与视黄酸受体相关孤儿受体（RORγ）相互作用并被其募集到Elovl 3启动子以激活转录。染色质免疫沉淀（ChIP）分析表明BRG 1与组蛋白乙酰转移酶p300相互作用以激活Elov 13的转录。通过siRNA消耗p300或通过姜黄素抑制p300减弱前列腺癌细胞中Elovl 3的反式激活。总之，我们的数据确定了一种新的表观遗传途径，将Elovl 3转录与前列腺癌细胞迁移和侵袭联系起来。
Prostate cancer malignancies are intimately correlated with deregulated fatty acid metabolism. The underlying epigenetic mechanism is not fully understood. In the present study we investigated the mechanism whereby the chromatin remodeling protein BRG1 regulates the transcription of long-chain fatty acid elongase 3 (Elovl3) in prostate cancer cells. We report that in response to pro-metastatic cues (androgen and TGF-β) BRG1 expression was up-regulated along with Elvol3 in prostate cancer cells. BRG1 over-expression potentiated whereas BRG1 knockdown attenuated prostate cancer cell migration and invasion. Coincidently, Elovl3 was up-regulated following BRG1 over-expression and down-regulated after BRG1 knockdown in prostate cancer cells. Further analysis revealed that BRG1 interacted with and was recruited by retinoic acid receptor-related orphan receptor (RORγ) to the Elovl3 promoter to activate transcription. Chromatin immunoprecipitation (ChIP) profiling demonstrated that BRG1 interacted with histone acetyltransferase p300 to activate Elovl3 transcription. Depletion of p300 by siRNA or inhibition of p300 by curcumin attenuated Elovl3 trans-activation in prostate cancer cells. Together, our data identify a novel epigenetic pathway that links Elovl3 transcription to prostate cancer cell migration and invasion.