Ubiquitous expressed transcript promotes tumorigenesis by acting as a positive modulator of the polycomb repressive complex 2 in clear cell renal cell carcinoma
Ubiquitous expressed transcript promotes tumorigenesis by acting as a positive modulator of the polycomb repressive complex 2 in clear cell renal cell carcinoma
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普遍表达的转录物通过作为透明细胞肾细胞癌中多梳抑制复合物2的正调节剂促进肿瘤发生
DOI：
10.1186/s12885-019-6069-3
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发表时间：
2019-09
期刊：
影响因子：
3.8
通讯作者：
Chen Zhiqiang
中科院分区：
文献类型：
--
作者：
Zeng Jin;Xiang Wei;Zhang Yucong;Huang Chunhua;Chen Ke;Chen Zhiqiang
背景无处不在的表达转录因子(UXT)通过调节包括雄激素受体(AR)在内的多种转录因子的转录活性，在多种肿瘤中发挥关键作用。然而，UXT在肾透明细胞癌(CcRCC)中的作用尚不清楚。方法采用双杂交筛选、GST下拉试验和免疫共沉淀法检测UXT的相互作用蛋白。用染色质免疫沉淀法检测HOXA9启动子上组蛋白H3赖氨酸27的三甲基化水平。CCK-8比色法、集落形成实验和Transwell实验检测肾癌细胞的增殖、集落形成、迁移和侵袭能力。结果Zust Homolog 2增强子(EZH2)是一种新的UXT相互作用蛋白，UXT与EZH2在细胞核内相互作用。此外，UXT与多梳抑制复合体2(PRC2)通过直接结合EZH2和ZEST 12同源物抑制物(SUZ12)而不是与胚胎外胚层发育蛋白(EED)相互作用。此外，UXT通过促进EZH2与SUZ12的结合来激活EZH2组蛋白甲基转移酶的活性。我们进一步提供了显著的证据表明，UXT的敲除以EZH2依赖的方式抑制肾癌细胞的增殖、克隆形成、迁移和侵袭。结论UXT是一种新的肾癌调控基因，可作为肾癌的癌基因，影响患者的预后。
BackgroundThe ubiquitous expressed transcript (UXT) plays a key role in various tumors by regulating transcriptional activity of multiple transcription factors, including androgen receptor (AR). However, the role of UXT in clear cell renal cell carcinoma (ccRCC) is still unknown.MethodsYeast two-hybrid screening, GST pull-down and co-immunoprecipitation assays were performed to detect the interacting protein of UXT. Chromatin immunoprecipitation (ChIP) was performed to investigate the levels of histone H3 lysine 27 trimethylation at the HOXA9 promoters. CCK-8 assays, colony formation assays and Transwell assays were performed to detect the proliferation, colony formation, migration and invasion of renal cancer cells. Quantitative PCR analysis was performed to detect the expressions of UXT in human ccRCC samples.ResultsThe enhancer of zeste homolog 2 (EZH2) is a novel UXT interacting protein and UXT interacts with EZH2 in the nucleus. In addition, UXT interacts with the polycomb repressive complex 2 (PRC2) through directly binding to EZH2 and suppressor of zeste 12 homolog (SUZ12), but not to embryonic ectoderm development (EED). Moreover, the UXT activates EZH2 histone methyltransferase activity by facilitating EZH2 binding with SUZ12. We further provided striking evidences that knockdown of UXT inhibits proliferation, colony formation, migration and invasion of renal cancer cells, in an EZH2-dependent manner. Importantly, the upregulation of UXT expression was observed in clinical ccRCC samples, and the high expression level of UXT was associated with advanced stage, distant metastasis and poor overall survival in patients with ccRCC.ConclusionThe UXT is a novel regulator of the PRC2 and acts as a renal cancer oncogene that affects the progression and survival of ccRCC patients.
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影响因子：
5.3
作者：
通讯作者：
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SF3B3 对 EZH2 前体 mRNA 的选择性剪接有助于肾癌的致瘤潜力
DOI：
10.1158/1078-0432.ccr-16-2020
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chen K;Xiao H;Zeng J;Yu G;Zhou H;Huang C;Yao W;Xiao W;Hu J;Guan W;Wu L;Huang J;Huang Q;Xu H;Ye Z
通讯作者：
Ye Z
DOI：
--
发表时间：
2018
期刊：
--
影响因子：
--
作者：
Paulo Rodrigues;Saroor A. A. Patel-Saroor-A.-A.-Patel-10127182;L. Harewood;Ioana Olan;E. Vojtasova;S. Syafruddin;M. N. Zaini;E. Richardson;Johanna Burge;A. Warren;G. Stewart;K. Saeb‐Parsy;S. Samarajiwa;Sakari Vanharanta
通讯作者：
Paulo Rodrigues;Saroor A. A. Patel-Saroor-A.-A.-Patel-10127182;L. Harewood;Ioana Olan;E. Vojtasova;S. Syafruddin;M. N. Zaini;E. Richardson;Johanna Burge;A. Warren;G. Stewart;K. Saeb‐Parsy;S. Samarajiwa;Sakari Vanharanta
UXT-AS1诱导的UXT选择性剪接与结直肠癌的肿瘤进展相关
影响因子：
5.3
作者：
Jun Yin;Wei Luo;Xiang Zeng;Lisi Zeng;Zhiyang Li;Xiaofang Deng;Xiaojun Tan;Weimin Hu
通讯作者：
Weimin Hu
影响因子：
3.3
作者：
Zhao, HW;Wang, Q;Greene, MI
通讯作者：
Greene, MI