HIF1A and hepatocellular carcinoma: Additionally, high HCC cell proliferation depletes the oxygen levels in the surrounding microenvironment and exacerbates local hypoxic conditions [94,96] A key transcription factor regulated in response to hypoxia, hypoxia-inducible factor-1α (HIF-1α), is significantly upregulated in HCC and correlates with poor patient outcome [45,97].