Figure 5.

Signaling pathways potentially impacted by IH in lung cancer. IH promotes lung cancer invasion and metastasis by upregulating EMT-related proteins through HIF-1α and ESM1, while HIF-1α enhances the properties of CSCs and increases ROS generation (especially mtROS), resulting in altered genetic material. IH can up-regulate the expression of PD-1 and TGF–β, consequently influencing the tumor immune microenvironment. At the same time, there is a mutual interaction between PD-1 and HIF-1α. IH enhances the expression of Nrf2 and Wnt/β-Catenin-related genes, leading to the up-regulation of their downstream target genes, such as VEGF, which promoted angiogenesis in lung cancer. IH up-regulates the expression of ALKBH5 in lung cancer, which led to the increase of FOXM1 protein level in tumor tissues.