HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target.
HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target.
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HDAC4 促进鼻咽癌进展并作为治疗靶点。
DOI：
10.1038/s41419-021-03417-0
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发表时间：
2021-02-01
影响因子：
9
通讯作者：
Sang Y
中科院分区：
文献类型：
--
作者：
Cheng C;Yang J;Li SW;Huang G;Li C;Min WP;Sang Y
组蛋白去乙酰化酶（HDACs）参与肿瘤进展，并且一些已成功地成为癌症治疗的靶点。组蛋白去乙酰化酶4（HDAC4）是一种IIa类HDAC，在我们之前的微阵列筛选中其表达上调。然而，HDAC4失调在鼻咽癌（NPC）中的作用以及肿瘤生长和转移的潜在机制仍然不清楚。在此，我们首先证实原发性和转移性鼻咽癌组织中的HDAC4水平与正常鼻咽上皮组织相比显著升高，并且发现HDAC4高表达预示着总生存期（OS）和无进展生存期（PFS）较差。在功能上，HDAC4加速细胞周期G1/S转换并诱导上皮 - 间质转化，从而在体外促进鼻咽癌细增殖、迁移和侵袭，在体内促进肿瘤生长和肺转移。有趣的是，敲低N - CoR消除了HDAC4对鼻咽癌细侵袭和迁移能力的影响。从机制上讲，HDAC3/4与E - 钙黏蛋白启动子结合以抑制E - 钙黏蛋白转录。我们还表明HDAC4抑制剂他喹莫德抑制鼻咽癌中的肿瘤生长。因此，HDAC4可能是鼻咽癌患者的一个潜在诊断标志物和治疗靶点。
Histone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated in our previous microarray screen. However, the role of HDAC4 dysregulation and mechanisms underlying tumor growth and metastasis in nasopharyngeal carcinoma (NPC) remain elusive. Here, we first confirmed that the HDAC4 levels in primary and metastatic NPC tissues were significantly increased compared with those in normal nasopharyngeal epithelial tissues and found that high HDAC4 expression predicted a poor overall survival (OS) and progression-free survival (PFS). Functionally, HDAC4 accelerated cell cycle G1/S transition and induced the epithelial-to-mesenchymal transition to promote NPC cell proliferation, migration, and invasion in vitro, as well as tumor growth and lung metastasis in vivo. Intriguingly, knockdown of N-CoR abolished the effects of HDAC4 on the invasion and migration abilities of NPC cells. Mechanistically, HDAC3/4 binds to the E-cadherin promoter to repress E-cadherin transcription. We also showed that the HDAC4 inhibitor tasquinimod suppresses tumor growth in NPC. Thus, HDAC4 may be a potential diagnostic marker and therapeutic target in patients with NPC.
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影响因子：
3.8
作者：
Wang Z;Qin G;Zhao TC
通讯作者：
Zhao TC
影响因子：
23.9
作者：
Lang, Charmaine;Campbell, Kieran R.;Wade-Martins, Richard
通讯作者：
Wade-Martins, Richard
影响因子：
5.4
作者：
Parra, Maribel
通讯作者：
Parra, Maribel
TEL2 通过下调 SERPINE1 抑制鼻咽癌转移。
影响因子：
--
作者：
Sang Y;Chen MY;Luo D;Zhang RH;Wang L;Li M;Luo R;Qian CN;Shao JY;Zeng YX;Kang T
通讯作者：
Kang T
影响因子：
9
作者：
Xiong, Yaoyi;Yuan, Lushun;Wang, Xinghuan
通讯作者：
Wang, Xinghuan