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

Although expression of MTA1 inversely correlates with the nuclear localization of ERα, the effect and molecular mechanism of ERα regulation of MTA1 remain unknown. 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 ERα in cell lines. We found that MTA1 gene regulation by ERα may be influenced by nuclear corepressors. The MTA1 promoter has three functional ER-element half-sites that lead to decreased MTA1 transcription and expression. ERα overexpression suppressed the proliferation and invasion of hepatocellular carcinoma cells (HCC). In addition, overexpression of MTA1 attenuated ERα-mediated suppression of the proliferation and invasion of HCC cells and tumor formation in vivo. These results suggested feedback regulation between ERα and MTA1. In summary, our results demonstrated that ERα suppressed proliferation and invasion of human HCC cells through downregulation of MTA1 transcription. Our study is an improved description of the mechanisms of the suppressive effect of ERα on HCCs, adding understanding to the gender disparity of HCC progression.

尽管MTA1的表达与ERα的核定位呈负相关，但ERα对MTA1的调控作用及其分子机制仍不清楚。 采用实时定量PCR和蛋白质印迹分析来测量MTA1的水平。分别通过EdU掺入试验和Transwell试验评估对肝癌细胞增殖和侵袭的影响。利用shRNA和双荧光素酶试验研究细胞系中MTA1和ERα之间的调控关系。 我们发现ERα对MTA1基因的调控可能受到核辅阻遏物的影响。MTA1启动子有三个功能性的雌激素反应元件半位点，导致MTA1转录和表达降低。ERα过表达抑制肝癌细胞（HCC）的增殖和侵袭。此外，MTA1的过表达减弱了ERα介导的对肝癌细胞增殖和侵袭以及体内肿瘤形成的抑制作用。这些结果表明ERα和MTA1之间存在反馈调节。总之，我们的结果表明ERα通过下调MTA1转录来抑制人肝癌细胞的增殖和侵袭。 我们的研究更好地阐述了ERα对肝癌的抑制作用机制，增进了对肝癌进展的性别差异的理解。