Expression of HIF-2α/EPAS1 in hepatocellular carcinoma

Abstract

HIF-2alpha/EPAS1 is expressed in most of HCC with capsular infiltration and portal vein invasion, which indicates a possible role of HIF-2alpha/EPAS1 in HCC metastasis.

Inhibition of ERN1 signaling enzyme affects hypoxic regulation

“…Moreover, the expression of ePaS1 gene was significantly correlated with tumor size, invasion, and necrosis as well as with VeGf gene expression, which supported the correlation of EPAS1 up-regulation with tumor angiogenesis [42].…”

“…Thus, transcription factor HOXC6 may contribute to suppression of proliferation rate of glioma cells without ERN1 signaling enzyme function. Moreover, the decreased expression level of aTf3 and ePaS1 genes in ERN1 knockdown glioma cells may also contribute to suppression of proliferation, because these transcription factors play an important role in the control of tumor growth [25,26,[37][38][39]42]. At the same time, blockade of ERN1 signaling enzyme function enhances the hypoxic regulation of aTf3 and ePaS1 gene expressions, but prospective studies are still needed to clarify the significance of these results.…”

MicroRNA‐383 is a tumor suppressor in human lung cancer by targeting endothelial PAS domain‐containing protein 1

“…For instance, in invasive bladder cancer, EPAS1 was found to be upregulated and potentially mediates bladder cancer progression in a subset of tumor‐associated macrophages . Furthermore, the expression of EPAS1 was also upregulated in metastatic HCC with capsular infiltration and portal vein invasion and was suggested to be used as a diagnostic tool and possibly a target in tumor progression and prognosis of HCC . In hypoxic colorectal cancer, inhibiting the DNA methylation of the EPAS1 regulatory region led to elevated EPAS1 expression, hinting a novel prognostic potential of EPAS1 in colorectal cancer .…”

Downregulating hypoxia‐inducible factor‐2α improves the efficacy of doxorubicin in the treatment of hepatocellular carcinoma

“…( 7 ) The recently identified HIF‐2 has emerged as another attractive target for combating the resistance of HCC to chemotherapy because it is specifically expressed in certain cell types, including hepatocytes, and has distinct transcriptional targets in certain organs, including the liver. ( 21,22 ) It has been shown that HIF‐2 is commonly overexpressed in human HCC specimens, ( 19,31 ) and that its expression is correlated with clinicopathological features and poor clinical outcome. ( 5,19,31 ) In the present study, we have demonstrated that HIF‐2 siRNA exerts its antitumor effect by downregulating the expression of HIF‐2α, VEGF, TGF‐α, and cyclin D1, resulting in inhibition of cell proliferation, tumor angiogenesis, and microvessel perfusion.…”