Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in hepatocellular carcinoma cells

Abstract This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells.