HDAC7 promotes the oncogenicity of nasopharyngeal carcinoma cells by miR-4465-EphA2 signaling axis
HDAC7 promotes the oncogenicity of nasopharyngeal carcinoma cells by miR-4465-EphA2 signaling axis
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HDAC7通过miR-4465-EphA2信号轴促进鼻咽癌细胞致癌性
DOI：
10.1038/s41419-020-2521-1
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发表时间：
2020-05-06
影响因子：
9
通讯作者：
Xiao, Zhi-Qiang
中科院分区：
文献类型：
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作者：
Li, Qi-Guang;Xiao, Ta;Xiao, Zhi-Qiang
HDAC 7在癌症中起着至关重要的作用，并且是几种HDAC抑制剂的主要药物靶标。然而，HDAC 7在鼻咽癌（NPC）中的作用和机制仍不清楚。在这项研究中，我们观察到HDAC 7在NPC组织中相对于正常鼻咽粘膜（NNM）组织显著上调，HDAC 7表达水平与NPC进展呈正相关，与患者预后呈负相关，并且HDAC 7敲低显著抑制NPC细胞的体外增殖、迁移和侵袭，以及小鼠中NPC异种移植物的生长，表明HDAC 7促进NPC的致瘤性。在机制上，HDAC 7通过上调EphA 2促进NPC细胞的体外增殖、迁移和侵袭，其中miR-4465介导HDAC 7调节EphA 2，EphA 2是miR-4465的直接靶基因。我们进一步表明，miR-4465在NPC组织中相对于NNM组织显著下调，并通过靶向EphA 2表达抑制NPC细胞的体外增殖、迁移和侵袭。此外，我们观察到HDAC 7、miR-4465和EphA 2在NPC组织中的表达是相关的。结果表明，HDAC 7通过下调miR-4465并随后上调EphA 2来促进NPC的致癌性，突出显示HDAC 7作为NPC的潜在治疗靶点。
HDAC7 plays a crucial role in cancers, and is the main drug target of several HDAC inhibitors. However, the role and mechanism of HDAC7 in nasopharyngeal carcinoma (NPC) are still unclear. In this study, we observed that HDAC7 was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa (NNM) tissues, HDAC7 expression levels were positively correlated with NPC progression and negatively correlated with patient prognosis, and HDAC7 knockdown dramatically inhibited the in vitro proliferation, migration, and invasion of NPC cells, and the growth of NPC xenografts in mice, indicating the HDAC7 promotes the oncogenicity of NPC. Mechanistically, HDAC7 promoted the in vitro proliferation, migration, and invasion of NPC cells by upregulating EphA2, in which miR-4465 mediated HDAC7-regulating EphA2, a direct target gene of miR-4465. We further showed that miR-4465 was significantly downregulated in the NPC tissues relative to NNM tissues, and inhibited the in vitro proliferation, migration, and invasion of NPC cells by targeting EphA2 expression. Moreover, we observed that the expressions of HDAC7, miR-4465, and EphA2 in NPC tissues were correlated. The results suggest that HDAC7 promotes the oncogenicity of NPC by downregulating miR-4465 and subsequently upregulating EphA2, highlighting HDAC7 as a potential therapeutic target for NPC.