Figure 4. JMJD2C regulates the transcription of HIF-1 target gene in hypoxic environment, and involves in cancer progression including proliferation, invasion, metastasis, and metabolic reprogramming in tumors.

In hypoxia, HIF-1α dimerizes with HIF-1β to form active HIF-1 complex. JMJD2C interacts with HIF-1α and promotes the transcriptional activation of HIF-1 targeting genes via demethylating di- and trimethylated H3K9. The HIF-1 targeting genes include BNIP3 (BCL2 Interacting Protein 3), PDK1 (Pyruvate Dehydrogenase Kinase 1), LDHA (Lactate Dehydrogenase A), SLC2A1 (Solute Carrier Family 2 Member 1), L1CAM (L1 Cell Adhesion Molecule), LOXL2 (Lysyl Oxidase Like 2), and PSA (prostate-specific antigen).