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

Jiang Y, Zhu Y, Wang X, Gong J, Hu C, Guo B, Zhu B, Li Y - Oncotarget (2015)

Bottom Line: Regulations between NF-κB and HIF-1 have not been adequately addressed in previous research.We also found that NF-κB p50 and p65 (RelA), but not c-Rel, bound the HIF-1a promoter, thus increasing its transcription.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

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.

No MeSH data available.


Related in: MedlinePlus

Hypoxia represses miR-93 and miR-199a-5p by downregulating Dicer1(A) The temporal expression of the Dicer1 protein in HepG2 cells under hypoxia for 0-24 h. (B) After HepG2 cells were transfected with shNC or shDicer1, and exposed to hypoxia for 0 h (N), 4 h (H4) or 24 h (H24), the levels of miR-93 and miR-199a-5p were assessed. The results were expressed as the mean±SEM of four independent experiments. *P < 0.05 and **P < 0.01 compared with shNC plus N; ##P < 0.01 compared with shNC plus H24.
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Figure 4: Hypoxia represses miR-93 and miR-199a-5p by downregulating Dicer1(A) The temporal expression of the Dicer1 protein in HepG2 cells under hypoxia for 0-24 h. (B) After HepG2 cells were transfected with shNC or shDicer1, and exposed to hypoxia for 0 h (N), 4 h (H4) or 24 h (H24), the levels of miR-93 and miR-199a-5p were assessed. The results were expressed as the mean±SEM of four independent experiments. *P < 0.05 and **P < 0.01 compared with shNC plus N; ##P < 0.01 compared with shNC plus H24.

Mentions: Dicer1, also known as endoribonuclease Dicer or helicase with an RNase motif, is an enzyme required for the maturation of the vast majority of miRNAs [21]. We observed a decreased expression level in Dicer1 protein under acute hypoxia, and a subsequently increased level at the prolonged intervals (Figure 4A). Knockdown of Dicer1 downregulated miR-93 and miR-199a-5p in normoxic and prolonged hypoxic HepG2 cells (Figures 4B and S4). These results indicate that acute hypoxia exposure decreased Dicer1 which contributed, at least partially, to the generation of miR-93 and miR-199a-5p.


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

Jiang Y, Zhu Y, Wang X, Gong J, Hu C, Guo B, Zhu B, Li Y - Oncotarget (2015)

Hypoxia represses miR-93 and miR-199a-5p by downregulating Dicer1(A) The temporal expression of the Dicer1 protein in HepG2 cells under hypoxia for 0-24 h. (B) After HepG2 cells were transfected with shNC or shDicer1, and exposed to hypoxia for 0 h (N), 4 h (H4) or 24 h (H24), the levels of miR-93 and miR-199a-5p were assessed. The results were expressed as the mean±SEM of four independent experiments. *P < 0.05 and **P < 0.01 compared with shNC plus N; ##P < 0.01 compared with shNC plus H24.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4496226&req=5

Figure 4: Hypoxia represses miR-93 and miR-199a-5p by downregulating Dicer1(A) The temporal expression of the Dicer1 protein in HepG2 cells under hypoxia for 0-24 h. (B) After HepG2 cells were transfected with shNC or shDicer1, and exposed to hypoxia for 0 h (N), 4 h (H4) or 24 h (H24), the levels of miR-93 and miR-199a-5p were assessed. The results were expressed as the mean±SEM of four independent experiments. *P < 0.05 and **P < 0.01 compared with shNC plus N; ##P < 0.01 compared with shNC plus H24.
Mentions: Dicer1, also known as endoribonuclease Dicer or helicase with an RNase motif, is an enzyme required for the maturation of the vast majority of miRNAs [21]. We observed a decreased expression level in Dicer1 protein under acute hypoxia, and a subsequently increased level at the prolonged intervals (Figure 4A). Knockdown of Dicer1 downregulated miR-93 and miR-199a-5p in normoxic and prolonged hypoxic HepG2 cells (Figures 4B and S4). These results indicate that acute hypoxia exposure decreased Dicer1 which contributed, at least partially, to the generation of miR-93 and miR-199a-5p.

Bottom Line: Regulations between NF-κB and HIF-1 have not been adequately addressed in previous research.We also found that NF-κB p50 and p65 (RelA), but not c-Rel, bound the HIF-1a promoter, thus increasing its transcription.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

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.

No MeSH data available.


Related in: MedlinePlus