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Oncotarget. 2015 Apr 20;6(11):9409-19.

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

Author information

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.

Abstract

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.

KEYWORDS:

HIF-1; NF-κB; hypoxia; miRNA

PMID:
25823824
PMCID:
PMC4496226
DOI:
10.18632/oncotarget.3352
[Indexed for MEDLINE]
Free PMC Article

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