EBF3 reactivation by inhibiting the EGR1/EZH2/HDAC9 complex promotes metastasis via transcriptionally enhancing vimentin in nasopharyngeal carcinoma
EBF3 reactivation by inhibiting the EGR1/EZH2/HDAC9 complex promotes metastasis via transcriptionally enhancing vimentin in nasopharyngeal carcinoma
复制标题
通过抑制 EGR1/EZH2/HDAC9 复合物重新激活 EBF3 通过转录增强波形蛋白促进鼻咽癌转移
DOI：
10.1016/j.canlet.2021.12.010
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发表时间：
2022-02-28
期刊：
影响因子：
9.7
通讯作者：
Xia, Yunfei
中科院分区：
文献类型：
--
作者：
Ding, Shirong;Wang, Xin;Xia, Yunfei
转移是鼻咽癌治疗失败的主要原因，也是鼻咽癌患者死亡的主要原因。然而，导致鼻咽癌转移的基因改变和分子机制尚不清楚。在此，我们对有或无转移的患者进行RNA测序，发现早期B细胞因子3（EBF 3）在有转移的样本中显著升高。EBF 3通过直接与Vimentin启动子结合并上调Vimentin的转录水平而促进肿瘤转移，而EGR 1/EZH 2/HDAC 9复合物通过维持H3 K27-Me 3在其启动子的高表达水平而使EBF 3表观遗传学沉默。鼻咽癌组织中EBF 3与Vimentin表达呈正相关。此外，EBF 3或Vimentin的高表达与不良的总体生存相关，而EBF 3和Vimentin的高表达与更显著的不良预后相关。因此，靶向EBF 3或稳定EGR 1/EZH 2/HDAC 9复合物的特异性药物可能是癌症转移的新治疗策略。
Metastasis is the major reason for treatment failure and accounts for cancer-related death in patients with nasopharyngeal carcinoma. However, the genetic alterations and molecular mechanisms that cause nasopharyngeal carcinoma metastasis are elusive. Herein, we performed RNA sequencing in patients with or without metastasis, and found that the early B-cell factor 3 (EBF3) was significantly elevated in the samples with metastasis. Mechanistically, EBF3 promoted metastasis by directly combining with the promoter of Vimentin and transcriptionally upregulating it. In addition, EBF3 was epigenetically silenced by EGR1/EZH2/HDAC9 complexes via sustaining the high level of H3K27-Me3 at its promoter. Clinically, there was a positive correlation between EBF3 and Vimentin in nasopharyngeal carcinoma tissues. Moreover, high expression of EBF3 or Vimentin was correlated with poor overall survival, while the combination of high EBF3 and Vimentin expression was associated with more significant poor prognosis. Therefore, specific agents targeting EBF3 or stabilizing the EGR1/EZH2/HDAC9 complex could be novel therapeutic strategies for cancer metastasis.