Guan Guo Fang, Fu Ze Ming, Zhang De Jun, Guo Ying Yuan, Guo Fang, Wan Yi Ning, Bai Jie, Zhao Ying
Department of Otolaryngology-Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130041, China.
World J Oncol. 2024 Dec;15(6):929-941. doi: 10.14740/wjon1994. Epub 2024 Dec 11.
The effectiveness of immune checkpoint therapy highlights the need to understand abnormal programmed cell death protein-1 (PD-1) expression in nasopharyngeal carcinoma (NPC), especially when treatments fail, or resistance develops. Interferon gamma (IFN-γ) signaling is crucial for regulating programmed cell death-ligand 1 (PD-L1) expression. Our study focuses on interferon gamma receptor 2 (IFNGR2), an essential part of the IFN-γ pathway, and its impact on malignant traits in NPC.
The expression levels of IFNGR2 and PD-L1 were accessed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). To understand the cellular phenotypic effects, small interfering RNA (siRNA)/short hairpin RNA (shRNA) knockdown techniques were used to evaluate cell viability, clonogenic survival, migration and invasion, immunohistochemistry, and tumor formation assays. The relationship between IFNGR2 and microRNAs (miRNAs)/circular RNAs (circRNAs) will be verified using methods such as circRNA stability assay, rescue, and dual-luciferase reporter assay.
IFNGR2 was significantly overexpressed in NPC, and its expression positively correlated with PD-L1 levels. This overexpression contributed to increased cell proliferation, migration, invasion, clonogenicity, and tumor growth. Additionally, we identified an oncogenic circular RNA, circ_001377, and uncovered a novel mechanism by which upregulation of circ_001377 competitively bound to miR-498-3p. This interaction reduced miR-498-3p's ability to target IFNGR2. As a result, the diminished miR-498-3p led to increased IFNGR2 expression, which subsequently activated the IFN-γ signaling pathway and drove abnormal PD-L1 expression.
IFNGR2 is an oncogenic factor in NPC. The circ_001377/miR-498-3p interaction drives IFNGR2 upregulation and PD-L1 overexpression, suggesting that targeting this axis could improve therapeutic outcomes.
免疫检查点疗法的有效性凸显了了解鼻咽癌（NPC）中程序性细胞死亡蛋白1（PD-1）异常表达的必要性，尤其是在治疗失败或出现耐药性时。干扰素γ（IFN-γ）信号传导对于调节程序性细胞死亡配体1（PD-L1）的表达至关重要。我们的研究聚焦于干扰素γ受体2（IFNGR2），它是IFN-γ通路的重要组成部分，及其对NPC恶性特征的影响。
使用定量逆转录聚合酶链反应（qRT-PCR）检测IFNGR2和PD-L1的表达水平。为了解细胞表型效应，采用小干扰RNA（siRNA）/短发夹RNA（shRNA）敲低技术评估细胞活力、克隆存活、迁移和侵袭、免疫组织化学及肿瘤形成试验。将使用诸如环状RNA稳定性测定、拯救和双荧光素酶报告基因测定等方法验证IFNGR2与微小RNA（miRNA）/环状RNA（circRNA）之间的关系。
IFNGR2在NPC中显著过表达，其表达与PD-L1水平呈正相关。这种过表达导致细胞增殖、迁移、迁移、侵袭、克隆形成能力及肿瘤生长增加。此外，我们鉴定出一种致癌环状RNA，即circ_001377，并揭示了一种新机制，即circ_001377的上调竞争性结合miR-498-3p。这种相互作用降低了miR-498-3p靶向IFNGR2的能力。结果，miR-498-3p减少导致IFNGR2表达增加，进而激活IFN-γ信号通路并驱动异常的PD-L1表达。
IFNGR2是NPC中的致癌因子。circ_001377/miR-498-3p相互作用驱动IFNGR2上调和PD-L1过表达，表明靶向该轴可能改善治疗效果。
