Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Department of Urology, the First Affiliated Hospital of Nanchang University, Nanchang, 330000, People's Republic of China.
BMC Cancer. 2019 Sep 3;19(1):874. doi: 10.1186/s12885-019-6069-3.
The 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.
Yeast 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.
The 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.
The UXT is a novel regulator of the PRC2 and acts as a renal cancer oncogene that affects the progression and survival of ccRCC patients.
普遍表达的转录本（UXT）通过调节多种转录因子的转录活性，包括雄激素受体（AR），在各种肿瘤中发挥关键作用。然而，UXT 在透明细胞肾细胞癌（ccRCC）中的作用尚不清楚。
进行酵母双杂交筛选、GST 下拉和共免疫沉淀实验以检测 UXT 的相互作用蛋白。进行染色质免疫沉淀（ChIP）实验以研究 HOXA9 启动子处组蛋白 H3 赖氨酸 27 三甲基化的水平。通过 CCK-8 实验、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。通过定量 PCR 分析检测人 ccRCC 样本中 UXT 的表达。
增强子的锌指蛋白 2（EZH2）是一种新型 UXT 相互作用蛋白，UXT 在核内与 EZH2 相互作用。此外，UXT 通过直接与 EZH2 和抑制素锌指蛋白 12 同源物（SUZ12）结合，而不是与胚胎外胚层发育（EED）结合，与多梳抑制复合物 2（PRC2）相互作用。此外，UXT 通过促进 EZH2 与 SUZ12 的结合，激活 EZH2 组蛋白甲基转移酶活性。我们进一步提供了令人信服的证据表明，UXT 敲低抑制肾癌细胞的增殖、集落形成、迁移和侵袭，这是一种依赖于 EZH2 的方式。重要的是，在临床 ccRCC 样本中观察到 UXT 表达上调，并且 UXT 的高表达水平与 ccRCC 患者的晚期、远处转移和不良总生存期相关。
UXT 是 PRC2 的新型调节剂，作为一种肾癌致癌基因，影响 ccRCC 患者的进展和生存。
