Mechanism of miR-760 Reversing Lung Cancer Immune Escape by Downregulating IDO1 and Eliminating Regulatory T Cells Based on Mathematical Biology

Abstract

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). Background. 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. Method. 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. Results. 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. Conclusion. 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.