Targeting EZH2 regulates tumor growth and apoptosis through modulating mitochondria dependent cell-death pathway in HNSCC.
Targeting EZH2 regulates tumor growth and apoptosis through modulating mitochondria dependent cell-death pathway in HNSCC.
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DOI：
10.18632/oncotarget.5606
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发表时间：
2015-10-20
期刊：
影响因子：
--
通讯作者：
Zhang L
中科院分区：
文献类型：
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作者：
Zhou X;Ren Y;Kong L;Cai G;Sun S;Song W;Wang Y;Jin R;Qi L;Mei M;Wang X;Kang C;Li M;Zhang L
EZH2是一种负预后因子，在包括头颈部鳞状细胞癌（HNSCC）在内的大多数人类癌症中过表达或活化。对癌症基因组图谱（TCGA）HNSCC数据的分析表明，EZH2过表达与高肿瘤分级相关，并赋予不良预后。EZH2抑制在体外触发细胞凋亡、细胞周期停滞和细胞生长减少。在HNSCC中，当EZH2表达被抑制时，MICU1（线粒体钙摄取1）被下调。当EZH 2和MICU 1受到抑制时，HNSCC细胞变得容易发生细胞周期停滞和细胞凋亡。线粒体膜电位和胞浆Ca2+浓度分析表明，EZH2和MICU1是维持线粒体膜电位稳定所必需的。使用异种移植肿瘤模型来证实EZH2消耗抑制HNSCC细胞生长并诱导肿瘤细胞凋亡。总之，EZH2是HNSCC中潜在的抗肿瘤靶点。
EZH2 is a negative prognostic factor and is overexpressed or activated in most human cancers including head and neck squamous cell carcinoma (HNSCC). Analysis of The Cancer Genome Atlas (TCGA) HNSCC data indicated that EZH2 over-expression was associated with high tumor grade and conferred poor prognosis. EZH2 inhibition triggered cell apoptosis, cell cycle arrest and decreased cell growth in vitro. MICU1 (mitochondrial calcium uptake1) was shown to be down regulated when EZH2 expression was inhibited in HNSCC. When the EZH2 and MICU1 were inhibited, HNSCC cells became susceptible to cell cycle arrest and apoptosis. Mitochondrial membrane potential and cytosolic Ca2+ concentration analysis suggested that EZH2 and MICU1 were required to maintain mitochondrial membrane potential stability. A xenograft tumor model was used to confirm that EZH2 depletion inhibited HNSCC cell growth and induced tumor cell apoptosis. In summary, EZH2 is a potential anti-tumor target in HNSCC.