Pulmonary and Critical Care Medicine, Zibo Central Hospital of Shandong Province, Zibo, 255000 Shandong, China.
Pneumology Department, Chengwu Hospital, Chengwu, China.
Comput Math Methods Med. 2022 Jul 14;2022:2960773. doi: 10.1155/2022/2960773. eCollection 2022.
In cancer biology, mathematical models have become indispensable. They are useful for gaining a mechanistic grasp of cancer's dynamic processes. In cancer research, mathematical modelling approaches are becoming more common. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments (Altrock et al., 2015). . MicroRNA-760 (miR-760), as an early discovered tumor suppressor gene, is poorly expressed in lung cancer (LC). Indoleamine 2,3-dioxygenase 1 (IDO1), as an important regulator of T cell function, is active in immune tolerance. We discovered that miR-760 has a targeted relationship with IDO1, but the regulatory mechanism between miR-760 and IDO1 is still unclear. . The miR-760 and IDO1 levels in NSCLC were tested via real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting (WB). Cell growth was tested by CCK8, and NSCLC cell migration and invasion were analyzed through Transwell analysis. The binding conditions and target gene of miR-451 in NSCLC cells were determined via double luciferase reporter gene. The CD8+ T and CD4+ T cell ratio in CD45+cells was assessed by flow cytometry. . qRT-PCR revealed that miR-760 was low-expressed and IDO2 was highly expressed in LC. miR-760 mimics suppressed cell growth, invasiveness, and migration. We also observed that miR-760 could downregulate the IDO1 protein level. Significantly, we revealed that miR-760 could inhibit CD8+ T cell apoptosis by controlling IDO1 enzyme function. . Our findings show that miR-760 inhibits CD8+ T cell responses in LC through regulating IDO1, laying the groundwork for the development of novel vaccination therapies for the treatment of LC.
在癌症生物学中，数学模型已变得不可或缺。它们对于理解癌症的动态过程具有重要意义。在癌症研究中，数学建模方法越来越普遍。癌症的复杂性非常适合采用定量方法，因为它为新的发展提供了挑战和机遇（Altrock 等人，2015 年）。. 微小 RNA-760（miR-760）作为早期发现的肿瘤抑制基因，在肺癌（LC）中表达水平较低。吲哚胺 2,3-双加氧酶 1（IDO1）作为 T 细胞功能的重要调节剂，在免疫耐受中具有活性。我们发现 miR-760 与 IDO1 具有靶向关系，但 miR-760 与 IDO1 之间的调节机制尚不清楚。. 通过实时定量聚合酶链反应（qRT-PCR）和蛋白质印迹（WB）检测 NSCLC 中的 miR-760 和 IDO1 水平。通过 CCK8 检测细胞生长，通过 Transwell 分析检测 NSCLC 细胞迁移和侵袭。通过双荧光素酶报告基因检测 miR-451 在 NSCLC 细胞中的结合条件和靶基因。通过流式细胞术评估 CD45+细胞中 CD8+T 和 CD4+T 细胞的比例。. qRT-PCR 显示 miR-760 在 LC 中低表达，IDO2 高表达。miR-760 模拟物抑制细胞生长、侵袭和迁移。我们还观察到 miR-760 可以下调 IDO1 蛋白水平。重要的是，我们揭示了 miR-760 通过控制 IDO1 酶功能抑制 LC 中 CD8+T 细胞凋亡。. 我们的研究结果表明，miR-760 通过调节 IDO1 抑制 LC 中 CD8+T 细胞的反应，为开发治疗 LC 的新型疫苗治疗方法奠定了基础。
