Temporal regulation of HIF-1 and NF-κB in hypoxic hepatocarcinoma cells
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Yuan Jiang1,*, Ying Zhu1,*, Xinxin Wang1,*, Juan Gong1, Chunyan Hu1, Bo Guo1, Bo Zhu1, Yongsheng Li1,2
1Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
2Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
*These authors have contributed equally to this work
Bo Zhu, e-mail: [email protected]
Yongsheng Li, e-mail: [email protected]
Keywords: hypoxia, NF-κB, HIF-1, miRNA
Received: December 01, 2014 Accepted: February 10, 2015 Published: March 19, 2015
Regulations between NF-κB and HIF-1 have not been adequately addressed in previous research. Here, we report that hypoxia increased NF-κB in hepatocellular carcinoma cells. The HIF-1 protein level was rapidly induced by protein stabilization (by 2 hours) and then moderately decreased, whereas mRNA levels were reciprocally increased. We also found that NF-κB p50 and p65 (RelA), but not c-Rel, bound the HIF-1a promoter, thus increasing its transcription. In contrast, miR-199a-5p and miR-93, c-Rel downstream targets, decreased HIF-1α at both the mRNA and protein levels. Dicer1, a key enzyme in miRNA biogenesis, was decreased by acute hypoxia but was later increased by HIF-1, rather than by the above-mentioned NF-κB subunits. Thus, NF-κB both positively and negatively fine-tuned HIF-1 in hypoxic hepatocarcinoma cells.
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