In a hypoxic environment, the accumulation of HIF-1α can regulate the expression of downstream genes through multiple mechanisms, facilitating tumor cell proliferation, angiogenesis, energy metabolism, epithelial–mesenchymal transition (EMT), immune escape, etc., thereby making tumor cells more tolerant of the HME and acquiring greater capabilities for proliferation, metastasis, and invasion42,44 (Fig. 3). This evidence concerns the gene HIF1A and neoplasm.