Inhibition of MTA1 by ERα contributes to protection hepatocellular carcinoma from tumor proliferation and metastasis

Background: Although expression of MTA1 inversely correlates with the nuclear localization of ER alpha, the effect and molecular mechanism of ER alpha regulation of MTA1 remain unknown. Methods: Quantitative real time PCR and western blot analyses were used to measure levels of MTA1. The effect on HCC cell proliferation and invasion was assessed by EdU incorporation assays and Transwell, respectively. ShRNA and dual-luciferase assays were used to investigate the regulatory relationship between MTA1 and ER alpha in cell lines. Results: We found that MTA1 gene regulation by ER alpha may be influenced by nuclear corepressors. The MTA1 promoter has three functional ER-element half-sites that lead to decreased MTA1 transcription and expression. ER alpha overexpression suppressed the proliferation and invasion of hepatocellular carcinoma cells (HCC). In addition, overexpression of MTA1 attenuated ER alpha mediated suppression of the proliferation and invasion of HCC cells and tumor formation in vivo. These results suggested feedback regulation between ER alpha and MTA1. In summary, our results demonstrated that ER alpha suppressed proliferation and invasion of human HCC cells through downregulation of MTA1 transcription. Conclusions: Our study is an improved description of the mechanisms of the suppressive effect of ER alpha on HCCs, adding understanding to the gender disparity of HCC progression.