Table 1.

Hypoxia-regulated genes involved in the regulation of the TME (Krock et al. 2011; Damgaci et al. 2018; Pietrobon and Marincola 2021)

Biological functions	Hypoxia/HIF target genes
Angiogenesis	VEGF, VEGFR-1, VEGFR-2, Angiopoietin-1, -2, Tie-2, ADM, FGF, PlGF, PDGF-B, SCF, Osteopontin, PAI-1, MMP, TIMP, NOS, COX-2, Endoglin, α1B-adrenergic receptor, Endothelin-1, Semaphorin 4D, Integrins, Leptin, Endosialin, Adenosine A2A receptor, Oxygen-regulated protein-150, SDF-1, Interleukins (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, DLL, CTGF, HO-1)
Apoptosis	p53, BNIP-3, NIX, BAX, RTP801/RED1, Ref-1, Bcl-2, NF-kB, HSP70, BID
Proliferation/survival	IGF-BP1-3, IGF2, CCD1, TGF-α/β, p21, cyclin G2, NOS2
Cell migration and invasion	CXCR4, MMP-2, LOX, PAI-1, c-Met, LRP1, MIC2/CD99, fibronectin, uPAR, Col V, AMF/GPI, CATHD, integrin-linked kinase, integrins
Therapeutic resistance	MDR-1
Immune evasion	PD-L1, CD39, CD47, SDF-1 (CXCL12), ET-1, ET-2, FOXP3, CCL28, IFN-γ, IL-2, Semaphorin 3A

ADM adrenomedullin, AMF autocrine motility factor, Ang-1/2 angiopoietin-1/2, Bcl-2 B-cell leukemia/lymphoma 2, BNIP3 Bcl-2 nineteen kilodalton interacting protein 3, CATHD cathepsin D, CCD1 coiled-coil-DIX1, CTGF connective tissue growth factor, COX-2 cyclooxygenase-2, CXCR4 CXC chemokine receptor 4, DLL delta-like ligand, HSP70 heat shock protein 70, FGF fibroblast growth factor, HO-1 heme oxygenase-1, IGF2 insulin-like growth factor 2, IGF-BP IGF factor binding protein, LOX lysyl oxidase, MIC2 microneme protein 2, MDR1 multidrug resistance 1, MMP2 matrix metalloproteinase 2, NF-κB nuclear factor kappa B, NOS2 nitric oxide synthase 2, TGF-α, β transforming growth factor-α, β, uPAR urokinase plasminogen activator receptor, PAI-1 plasminogen activator inhibitor-1, PD-L1, PlGF placenta growth factor, PDGF-B platelet-derived growth factor beta, SCF stem cell factor, SDF-1 stromal-derived growth factor, Tie-2 TEK tyrosine kinase endothelial, TIMP tissue inhibitor of metalloproteinases, VEGF vascular endothelial growth factor, VEGF-R VEGF receptor