Ubiquitin C-terminal hydrolase L1 promotes expression of programmed cell death-ligand 1 in non-small-cell lung cancer cells
Ubiquitin C-terminal hydrolase L1 promotes expression of programmed cell death-ligand 1 in non-small-cell lung cancer cells
复制标题
泛素C末端水解酶L1促进非小细胞肺癌细胞中程序性细胞死亡配体1的表达
DOI：
10.1111/cas.14529
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发表时间：
2020-07-06
期刊：
影响因子：
5.7
通讯作者：
Shi, Yongyu
中科院分区：
文献类型：
--
作者：
Mao, Rudi;Tan, Xiao;Shi, Yongyu
程序性细胞死亡配体1（PD-L1）在非小细胞肺癌（NSCLC）中的表达可引起免疫逃逸。阐明PD-L1表达的调控机制是建立新的肿瘤免疫治疗策略的前提。泛素C末端水解酶L1（UCHL 1）是细胞信号转导的调节因子，在NSCLC中异常表达。然而，尚不清楚UCHL 1是否调节NSCLC细胞中PD-L1的表达。在本研究中，我们发现UCHL 1促进NSCLC细胞系中PD-L1的表达。此外，在体外实验中，NSCLC细胞中表达的UCHL 1通过上调PD-L1表达来抑制Jurkat细胞的活化。此外，UCHL 1通过促进AKT-P65信号通路的激活来上调PD-L1表达。总之，这些结果表明UCHL 1促进NSCLC细胞中PD-L1的表达。这一发现表明，抑制UCHL 1可能通过下调NSCLC细胞中PD-L1的表达来抑制NSCLC的免疫逃逸。
Programmed cell death-ligand 1 (PD-L1) expressed on cancer cells can cause immune escape of non-small-cell lung cancer (NSCLC). Elucidation of the regulatory mechanisms of the PD-L1 expression is a prerequisite for establishing new tumor immunotherapy strategies. Ubiquitin C-terminal hydrolase L1 (UCHL1) is a regulator of cellular signaling transduction that is aberrantly expressed in NSCLC. However, it is not known whether UCHL1 regulates the expression of PD-L1 in NSCLC cells. In the present study, we found that UCHL1 promotes the expression of PD-L1 in NSCLC cell lines. In addition, UCHL1 expressed in NSCLC cells inhibited activation of Jurkat cells through upregulation of PD-L1 expression in in vitro experiments. Moreover, UCHL1 upregulates PD-L1 expression through facilitating activation of the AKT-P65 signaling pathway. In conclusion, these results indicated that UCHL1 promoted PD-L1 expression in NSCLC cells. This finding implied that inhibition of UCHL1 might suppress immune escape of NSCLC through downregulation of PD-L1 expression in NSCLC cells.