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

• Published in: Biomedicine & pharmacotherapy 2018-08, Vol.104, p.204-210
• Main Authors: Li, Jian-Wang, Huang, Chun-Zhen, Li, Jian-Hua, Yuan, Jian-Hua, Chen, Qiong-Hui, Zhang, Wei-Fang, Xu, Zhen-Sheng, Liu, Ying-Ping, Li, Yong, Zhan, Mei-Xiao, Lu, Li-Gong
• Format: Article
• Language: English
• Subjects: 5-FU; E-cadherin; Hepatocellular carcinoma; Methylation; Six2
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.05.032

[Display omitted] •A new critical role of six2 in hepatocellular carcinoma progression is proposed.•The mechanisms of six2 in hepatocellular carcinoma progression are further studied.•A novel mode of regulation of E-cadherin by six2 in hepatocellular carcinoma cells.•The novel mechanism provides new potential targets for hepatocellular carcinoma. 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.