PDF(Pubmed)
Abstract：
Non-small cell lung cancer (NSCLC) has constituted over 80% of the lung cancer population with a poor prognosis. Over the past decade, immunotherapy has been constructed in the enlargement of immune checkpoint inhibitors as a promising approach for NSCLC treatment. Evading the immune system using the PD-1/PD-L1 axis is an intelligent way for cancers, and T cells cannot respond fully and confront cancer. Recently, the miR-138 was reported as a PD-L1 regulator in NSCLC. However, its inhibitory impact on T-cell exhaustion has not been characterized. The present study aims to impair PD-L1 (B7-H1) expression in Adenocarcinoma cell lines using miR-138-5p and determines how it prevents Jurak cell exhaustion. To gain the purpose, first, 18 highly significant dysregulated miRNAs containing hsa-miR-138 and CD274-mRNA network were detected in NSCLC based on bioinformatics analysis. Moreover, our study revealed a high level of miR-138-5p could make significant changes like PDL1 downregulation, proliferation, and mortality rate in A549/Calu6 cells. We also simulate cancer environmental conditions by culturing Jurak cells and NSCLC cell lines under the influence of stimulator cytokines to show how miR-138-5p survives Jurak cells by targeting PD-L1/PD-1pathway.
摘要：
非小细胞肺癌（NSCLC）占预后不良的肺癌人群的80％以上。在过去的十年里，免疫疗法已在扩大免疫检查点抑制剂中被构建为NSCLC治疗的有希望的方法。使用PD-1/PD-L1轴逃避免疫系统是治疗癌症的一种智能方法，T细胞不能完全反应并对抗癌症。最近,miR-138在NSCLC中被报道为PD-L1调节因子.然而,其对T细胞耗竭的抑制作用尚未被表征。本研究旨在使用miR-138-5p削弱腺癌细胞系中的PD-L1（B7-H1）表达，并确定其如何防止Jurak细胞衰竭。为了达到目的，首先,基于生物信息学分析，在NSCLC中检测到18个含有hsa-miR-138和CD274-mRNA网络的高度失调的miRNA。此外，我们的研究表明，高水平的miR-138-5p可以像PDL1下调一样发生显著变化，扩散,和死亡率在A549/Calu6细胞。我们还通过在刺激细胞因子的影响下培养Jurak细胞和NSCLC细胞系来模拟癌症环境条件，以显示miR-138-5p如何通过靶向PD-L1/PD-1途径使Jurak细胞存活。
