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


ABSTRACT: Regulations between NF-?B and HIF-1 have not been adequately addressed in previous research. Here, we report that hypoxia increased NF-?B 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-?B 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-1? 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-?B subunits. Thus, NF-?B both positively and negatively fine-tuned HIF-1 in hypoxic hepatocarcinoma cells.

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC4496226 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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

Jiang Yuan Y   Zhu Ying Y   Wang Xinxin X   Gong Juan J   Hu Chunyan C   Guo Bo B   Zhu Bo B   Li Yongsheng Y  

Oncotarget 20150401 11


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  ...[more]

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