EZH2 regulates PD-L1 expression via HIF-1α in non-small cell lung cancer cells
EZH2 regulates PD-L1 expression via HIF-1α in non-small cell lung cancer cells
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EZH2 通过 HIF-1α 调节非小细胞肺癌细胞中 PD-L1 的表达
DOI：
10.1016/j.bbrc.2019.07.039
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Chen Degao
中科院分区：
文献类型：
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作者：
Zhao Yuetao;Wang XinXin;Wu Wei;Long Haixia;Huang Jiani;Wang Zhongyu;Li Tao;Tang Shu;Zhu Bo;Chen Degao
肺癌是最常见的被诊断的癌症，也是全世界大多数与癌症相关的死亡原因。程序性死亡配体1(PD-L1)的高表达是促进肺癌免疫逃逸、加重化疗耐药和预后不良的重要因素。因此，了解PD-L1在肺癌中的调控机制对肿瘤免疫治疗至关重要。Zust同源增强子2(EZH2)是一种具有组蛋白甲基转移酶活性的表观遗传调节分子，可促进免疫抑制微环境的形成。本研究旨在探讨EZH2在PD-L1表达中的作用及其在肺癌发生发展中的作用。我们发现EZH2在肺癌组织中表达上调，且与PD-L1水平呈正相关，预后不良。此外，表达shRNA的慢病毒介导的EZH2基因敲除抑制了PD-L1的mRNA和蛋白表达水平，从而通过增强抗肿瘤免疫反应延缓了体内肺癌的进展。此外，EZH2对PD-L1的调节作用依赖于HIF-1α。本研究结果表明，EZH2通过HIF-1α调节免疫抑制分子PD-L1在非小细胞肺癌细胞中的表达。
Lung cancer is the most commonly diagnosed cancer and accounts for most cancer-related mortalities worldwide. The high expression of programmed death ligand 1 (PD-L1) is an important factor that promotes immune escape of lung cancer, thus aggravates chemotherapy resistance and poor prognosis. Therefore, understanding the regulatory mechanism of PD-L1 in lung cancer is critical for tumor immunotherapy. Enhancer of Zeste homolog2 (EZH2), an epigenetic regulatory molecule with histone methyltransferase activity, promotes the formation of an immunosuppressive microenvironment. This study aimed to investigate the role of EZH2 in PD-L1 expression and in the progression of lung tumors. We found that EZH2 was upregulated in lung cancer tissues and positively correlated with PD-L1 levels and poor prognosis. Further, shRNA-expressing lentivirus mediated EZH2 knockdown suppressed both the mRNA and protein expression level of PD-L1, thus delaying lung cancer progression in vivo by enhancing anti-tumor immune responses. Moreover, the regulatory effect of EZH2 on PD-L1 depended on HIF-1α. The present results indicate that EZH2 regulates the immunosuppressive molecule PD-L1 expression via HIF-1α in non-small cell lung cancer cells.