Silencing HSF4 can inhibit the proliferation of HCC cells

Abstract Purpose: To explore the regulatory role of HSF4 in hepatocellular carcinoma stemness property maintaining and analysis the clinical significance of HSF4 in hepatocellular carcinoma. Materials and methods: Tumor spheroid formation assay was conducted to assess stemness property and enrich hepatocellular carcinoma stem-like cells. qRT-PCR and Western Blot was used to detect genes mRNA and protein expression level. KM-plotter database wad used to analyze the correlation between HSF4 and overall survival (OS) in HCC patients. Result: mRNA level of HSF4, as well as stemness-associated genes, was significantly higher in hepatocellular carcinoma tissue then in adjacent normal tissue. Positive correlation between expression level of HSF4 and SOX (r=0.1668, p<0.05), NANOG (r=0.7, p<0.05), POUSF1(r=0.7362, p<0.05), CD44(r=0.0128, p<0.05) was observed. The KM plotter showed that there is no significant difference between HSF4 high patients and HF4 low patients in term of overall survival (OS)(p=0.48). However, significant difference in terms of progression-free survival (PFS)(p=0.019) and relapse-free survival (RFS)(p=0.005) between these two groups was observed. In vitro assay results also suggest the positive correlation between HSF4 and stemness-associated genes. Increased HSF4 expression confers HCC enhanced tumor spheroid formation ability. Conclusion: HSF4 is significantly increased in liver cancer stem-like cells, indicating the possible contribution of HSF4 to stemness properties maintenance in liver cancer stem-like cells. Silencing HSF4 inhibits proliferation of hepatoma cells.