NME4 modulates PD-L1 expression via the STAT3 signaling pathway in squamous cell carcinoma.
NME4 modulates PD-L1 expression via the STAT3 signaling pathway in squamous cell carcinoma.
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DOI：
10.1016/j.bbrc.2020.03.055
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发表时间：
2020-03
影响因子：
3.1
通讯作者：
Shutao Zheng;Qing Liu;Tao Liu;Lifei Yang;Qiqi Zhang;Tongxue Shen;Xiao Zhang;Xiujuan Han;Xiaomei Lu
中科院分区：
文献类型：
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作者：
Shutao Zheng;Qing Liu;Tao Liu;Lifei Yang;Qiqi Zhang;Tongxue Shen;Xiao Zhang;Xiujuan Han;Xiaomei Lu
NME4，又称Nm23-H4，是NME/NM23核苷二磷酸激酶4的缩写，其主要作用是合成核苷三磷酸。然而，它与程序性死亡配体1(PD-L1)的关系仍远未被了解。在此，发现沉默NME4可以导致PD-L1的显著下调，在体外培养的食管鳞癌(ESCC)细胞系中，第705位丝氨酸的磷酸化STAT3被失活。为了进一步验证在细胞系中观察到的NME4和PD-L1之间的相关性，对GEPIA数据库中获得的宫颈鳞癌(CSCC)中NME4和PD-L1的转录RNA测序数据进行了Pearson相关分析。结果表明，CSCC中NME4和PD-L1的表达呈显著负相关。据我们所知，这是第一个描述NME4在鳞状细胞癌背景下对PD-L1的调节作用的报告，强烈暗示了NME4在阻止CD8 T细胞渗透到鳞癌微环境中的潜在作用。
NME4, also named Nm23-H4, is a contraction of NME/NM23 Nucleoside Diphosphate Kinase 4, whose major role is the synthesis of nucleoside triphosphates. However, its association with programmed death ligand 1 (PD-L1) remains far from understood. Herein, it was discovered that silencing NME4 can lead to the marked downregulation of PD-L1, with phosphorylated STAT3 at the 705th serine being inactivatedin vitroin esophageal squamous cell carcinoma (ESCC) cell lines. To further validate the association between NME4 and PD-L1 that was observed in cell lines, Pearson correlation analysis was performed on the data regarding the transcriptomic RNA sequencing of NME4 and PD-L1 in cervical squamous cell carcinoma (CSCC), which pathologically highly resembles ESCC in terms of tumor origin, obtained from the GEPIA database. It was demonstrated that their correlation was significant but negative between NME4 and PD-L1 in CSCC. To the best of our knowledge, this is the first report describing a modulation exerted by NME4 over PD-L1 in the background of squamous cell carcinoma, strongly suggestive of the underlying role of NME4 working to exclude CD8 T cells from infiltrating into the squamous cell carcinoma microenvironment.