Department of Respiratory, The First Hospital of Qinhuangdao, Qinhuangdao 066000, P.R. China.
Graduate School of Zunyi Medical University, Zunyi 563006, P.R. China.
Hum Mol Genet. 2022 Nov 28;31(23):4094-4106. doi: 10.1093/hmg/ddac155.
High-throughput circular RNA (circRNA) sequencing identified circRNA_001678 (circ_001678) as an upregulated circRNA in non-small cell lung cancer (NSCLC) tissues. Hence, the current study sought to investigate the function and the underlying mechanism of circRNA_001678 in immune escape of NSCLC. Briefly, commercially purchased NSCLC cell lines were adopted for in vitro experiment to evaluate the effects of circ_001678 over-expression or knockdown on cell biological functions, including proliferation, migration and invasive abilities. In addition, the effects of circ_001678 on the in vivo tumorigenicity ability were evaluated for verification. Accordingly, we uncovered that circ_001678 over-expression augmented NSCLC progression in vitro and enhanced tumorigenicity ability in vivo. The interaction between circ_001678 and miR-326 predicted online was verified by means of luciferase and RNA pull-down assays. Furthermore, circ_001678 could sponge miR-326 to up-regulate ZEB1. On the other hand, the tumor-promoting effects of circ_001678 could be inhibited by anti-PD-L1/PD-1 treatment. Mechanistically, circ_001678 led to the activation of the PD-1/PD-L1 pathway to promote CD8+ T cell apoptosis, thereby inducing NSCLC cell immune escape via regulation of the miR-326/ZEB1 axis. To conclude, our findings revealed that circ_001678 sponges miR-326 to up-regulate ZEB1 expression and induce the PD-1/PD-L1 pathway-dependent immune escape, thereby promoting the malignant progression of NSCLC.
高通量环状 RNA（circRNA）测序鉴定出环状 RNA_001678（circ_001678）在非小细胞肺癌（NSCLC）组织中上调。因此，本研究旨在探讨 circRNA_001678 在 NSCLC 免疫逃逸中的功能和潜在机制。简而言之，采用商业购买的 NSCLC 细胞系进行体外实验，以评估 circ_001678 过表达或敲低对细胞生物学功能的影响，包括增殖、迁移和侵袭能力。此外，还评估了 circ_001678 对体内致瘤能力的影响以进行验证。结果表明，circ_001678 过表达增强了 NSCLC 的体外进展，并增强了体内致瘤能力。circ_001678 与 miR-326 的相互作用通过荧光素酶和 RNA 下拉实验进行了验证。此外，circ_001678 可以吸附 miR-326 来上调 ZEB1。另一方面，circ_001678 的促瘤作用可以通过抗 PD-L1/PD-1 治疗来抑制。机制上，circ_001678 导致 PD-1/PD-L1 通路激活，促进 CD8+T 细胞凋亡，从而通过调节 miR-326/ZEB1 轴诱导 NSCLC 细胞免疫逃逸。总之，我们的研究结果表明，circ_001678 通过吸附 miR-326 来上调 ZEB1 的表达，并诱导 PD-1/PD-L1 通路依赖性免疫逃逸，从而促进 NSCLC 的恶性进展。
