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Background/aims

Hypoxia promotes the progression and metastasis of hepatocellular carcinoma (HCC). Hypoxia inducible factor-α (HIF-1α) regulates the expression of various chemokines involved in tumor growth, angiogenesis and metastasis.

Methods

The role of HIF-1α in HCC tumor growth and invasion and the prognosis of patients with HCC was investigated in cell lines and patient samples. HIF-1α mRNA and protein levels were assessed by qRT-PCR and western blotting. Silencing of HIF-1α downregulated the expression of granulocyte chemotactic protein-2 (GCP-2)/CXCL6, a CXC ELR+ chemokine, in HCC cells, and a luciferase assay showed that HIF-1α binds to a hypoxia response element in the promoter of CXCL6 and regulates its transcription. Induction of HIF-1α by hypoxia promoted the migration and invasion of HCC cells in vitro, and this effect was suppressed by an anti-CXCL6 antibody.

Results

HIF-1α is upregulated in HCC cell lines and tissues and its effect on promoting invasion and metastasis is mediated by its direct interaction with the pro-angiogenic chemokine CXCL6. CXCL6 expression was associated with poor prognosis of HCC patients.

Conclusion

HIF-1α promotes HCC progression and metastasis by upregulating CXCL6 transcription in HCC cells, providing a potential novel therapeutic target for the treatment of HCC."xsd:string
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http://purl.uniprot.org/citations/25323032http://purl.uniprot.org/core/author"Huang P."xsd:string
http://purl.uniprot.org/citations/25323032http://purl.uniprot.org/core/author"Tang W."xsd:string
http://purl.uniprot.org/citations/25323032http://purl.uniprot.org/core/author"Tian H."xsd:string
http://purl.uniprot.org/citations/25323032http://purl.uniprot.org/core/author"Zhao Z."xsd:string
http://purl.uniprot.org/citations/25323032http://purl.uniprot.org/core/author"Xia J."xsd:string
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http://purl.uniprot.org/citations/25323032http://purl.uniprot.org/core/pages"1536-1546"xsd:string
http://purl.uniprot.org/citations/25323032http://purl.uniprot.org/core/title"HIF-1alpha plays a role in the chemotactic migration of hepatocarcinoma cells through the modulation of CXCL6 expression."xsd:string
http://purl.uniprot.org/citations/25323032http://purl.uniprot.org/core/volume"34"xsd:string
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