Temporal regulation of HIF-1 and NF-κB in hypoxic hepatocarcinoma cells

// Yuan Jiang 1, * , Ying Zhu 1, * , Xinxin Wang 1, * , Juan Gong 1 , Chunyan Hu 1 , Bo Guo 1 , Bo Zhu 1 , Yongsheng Li 1, 2 1 Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China 2 Center 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 Correspondence to: Bo Zhu, e-mail: b.davis.zhu@gmail.com Yongsheng Li, e-mail: yongshengli2005@163.com Keywords: hypoxia, NF-κB, HIF-1, miRNA Received: December 01, 2014      Accepted: February 10, 2015      Published: March 19, 2015 ABSTRACT Regulations between NF- κ B 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.