Yu Hongwei, Zhang Yibin, Yang Rufei, Xie Changbin, Liao Zhiwei, Zhou Tongchong
Department of Radiotherapy, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
Oncol Lett. 2024 Dec 31;29(3):112. doi: 10.3892/ol.2024.14858. eCollection 2025 Mar.
Programmed death ligand 1 (PD-L1), an important immune checkpoint molecule, is abnormally activated in non-small cell lung cancer (NSCLC), which can interact with programmed death 1 to aid cancer cells in evading immune surveillance. Furthermore, tumor driver genes may be involved in the occurrence and development of NSCLC and have a potential role in PD-L1-mediated immune escape mechanisms. Therefore, the present study aimed to assess the behavioral and regulatory mechanisms by which circular RNA ENTPD7 (circENTPD7; hsa_circ_0019421) induces an immune response in the progression of NSCLC cells. In brief, circENTPD7, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and PD-L1 expression were assessed using reverse transcription-quantitative PCR, and IGF2BP2 and PD-L1 protein expression levels were evaluated using western blotting. Subsequently, the proliferation, migration, invasion and immune escape of NSCLC cells were assessed using a Cell Counting Kit-8 assay, Transwell assay, T cell co-culture assay, FITC ester assay, flow cytometry and ELISA. The experimental results revealed that circENTPD7, IGF2BP2 and PD-L1 levels were significantly elevated in NSCLC cells. CircENTPD7 knockdown suppressed the malignant phenotype of NSCLC cells, whereas overexpression of IGF2BP2 counteracted these effects, indicating that circENTPD7 contributed to the proliferation and metastasis of NSCLC cells by upregulating IGF2BP2. Furthermore, overexpression of IGF2BP2 accelerated the proliferation, metastasis and immune escape processes of NSCLC cells by upregulating PD-L1. Collectively, the results indicate that circENTPD7 contributes to the malignant progression of NSCLC cells by modulating the IGF2BP2/PD-L1 axis-mediated immune escape.
程序性死亡配体1（PD-L1）是一种重要的免疫检查点分子，在非小细胞肺癌（NSCLC）中异常激活，它可与程序性死亡1相互作用，帮助癌细胞逃避免疫监视。此外，肿瘤驱动基因可能参与NSCLC的发生和发展，并在PD-L1介导的免疫逃逸机制中发挥潜在作用。因此，本研究旨在评估环状RNA ENTPD7（circENTPD7；hsa_circ_0019421）在NSCLC细胞进展过程中诱导免疫反应的行为和调控机制。简而言之，使用逆转录定量PCR评估circENTPD7、胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）和PD-L1的表达，并使用蛋白质免疫印迹法评估IGF2BP2和PD-L1蛋白表达水平。随后，使用细胞计数试剂盒-8检测、Transwell检测、T细胞共培养检测、FITC酯检测、流式细胞术和酶联免疫吸附测定法评估NSCLC细胞的增殖、迁移、侵袭和免疫逃逸。实验结果显示，NSCLC细胞中circENTPD7、IGF2BP2和PD-L1水平显著升高。circENTPD7敲低抑制了NSCLC细胞的恶性表型，而IGF2BP2的过表达抵消了这些作用，表明circENTPD7通过上调IGF2BP2促进NSCLC细胞的增殖和转移。此外，IGF2BP2的过表达通过上调PD-L1加速了NSCLC细胞的增殖、转移和免疫逃逸过程。总体而言，结果表明circENTPD7通过调节IGF2BP2/PD-L1轴介导的免疫逃逸促进NSCLC细胞的恶性进展。
