Upregulation of hypoxia-inducible factor 1α mRNA expression was associated with poor prognosis in patients with hepatocellular carcinoma

Background: HIF1 alpha mRNA expression in hepatocellular carcinoma (HCC) tissues and its relationship with the prognosis in HCC patients is still unclear. We performed this study to investigate the expression of HIF1 alpha mRNA and its correlation with the prognosis in HCC patients. Materials and methods: GSE14520 and Oncomine database were used to analyse the differential expression of HIF1 alpha mRNA among HCC tissues and corresponding peritumour tissues or normal liver tissues. The relationship between HIF1 alpha mRNA expression and the clinicopathological features and survival in HCC patients was analysed using the GSE14520 dataset. CCK-8 assay, wound-healing assay, transwell invasion assay, tube formation assay, and subcutaneous xenograft tumour assays using nude mice were used to confirm the function of HIF1 alpha. Results: Expression of HIF1 alpha mRNA was significantly upregulated in HCC tissues (P<0.05 in all cases); this was supported by the results of the Western blotting (P=0.031) and IHC analyses. Our analysis of the clinicopathological features of HCC patients indicated that high HIF1 alpha mRNA expression was strongly related with TNM stage III (P=0.002) and BCLC stage C (P=0.038). Survival analysis demonstrated that HCC patients with high HIF1 alpha mRNA expression had a short overall survival (OS) (P=0.048), but showed no significant difference in recurrence-free survival (RFS) (P=0.066) compared to patients with low HIF1 alpha mRNA expression. We further demonstrated that HIF1 alpha promoted the proliferation, migration, invasion, and angiogenic ability of HCC cells, by using the stably transformed SK-Hepl and Hep-3B cell lines showing HIF1 alpha overexpression. Finally, xenograft tumour models of nude mice showed that RNA interference-mediated HIF1 alpha silencing suppressed tumour growth and angiogenesis in HCC. Conclusion: Our study suggests that the upregulation of HIF1 alpha mRNA, which is found in HCC tissues and associated with poor prognosis in HCC patients, contributed to the proliferation, migration, invasion, and angiogenic ability of HCC cells.