Expression of hypoxia‑inducible factor 3α in hepatocellular carcinoma and its association with other hypoxia‑inducible factors

Liu,Ping; Fang,Xiefan; Song,Yang; Jiang,Jian‑Xin; He,Qian‑Jin; Liu,Xiang‑Jie

doi:10.3892/etm.2016.3193

June-2016 Volume 11 Issue 6

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June-2016 Volume 11 Issue 6

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Article

Expression of hypoxia‑inducible factor 3α in hepatocellular carcinoma and its association with other hypoxia‑inducible factors

Authors:
- Ping Liu
- Xiefan Fang
- Yang Song
- Jian‑Xin Jiang
- Qian‑Jin He
- Xiang‑Jie Liu
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Affiliations: Department of Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA, Department of Pharmacy, Mercy Medical Center‑Clinton, Clinton, IA 52732, USA, Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550001, P.R. China, Department of General Surgery, The Center Hospital of Huanggang, Huanggang, Hubei 438000, P.R. China, Department of Rehabilitation, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China
Pages: 2470-2476
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Published online on: March 24, 2016

https://doi.org/10.3892/etm.2016.3193
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Abstract

The functional role of hypoxia-inducible factor (HIF)-3α in the development of hepatocellular carcinoma (HCC) is not yet fully understood. The aim of the present study was to elucidate the association between HIF‑3α expression and the clinicopathological features as well as prognosis of HCC patients. In addition, we investigated the association between HIF‑3α expression and the expression of HIF‑1α and HIF‑2α in tumor tissues. The protein levels of HIF‑3α were determined using immunohistochemical analysis of paraffin sections of 126 paired HCC and peritumoral tissues. PLC/PRF/5 cells, a human HCC cell line, were transfected with HIF‑1α and HIF‑2α vectors and HIF‑3α mRNA and protein expression was detected using quantitative polymerase chain reaction and western blot analysis, respectively. The expression of HIF‑3α was upregulated in 46.0% (58/126) and downregulated in 42.9% (54/126) of tumor tissues, respectively, when compared to peritumoral tissues. HIF‑3α protein expression was not associated with peripheral blood vessel invasion, overall survival, or disease‑free survival in HCC patients (P>0.05). In HCC tissues, the levels of HIF‑3α protein were positively correlated with HIF‑2α, but not with HIF‑1α expression in HCC tissues. HIF‑3α was upregulated in PLC/PRF/5 and Hep3B cells overexpressed with HIF‑1α or HIF‑2α. The hypoxic microenvironment of liver cancer did not lead to elevated HIF‑3α protein expression, indicating that HIF‑3α is regulated differently from HIF‑1α in vivo. The correlation between HIF‑3α and HIF‑2α expression at the cellular and tissue levels indicated that HIF‑3α may be a target gene of HIF‑2α. The hypoxic microenvironment did not lead to elevation of HIF‑3α protein expression in liver cancer; thus, HIF‑3α may be a target gene of HIF‑2α.

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