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 ERα, the effect and molecular mechanism of ERα 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 ERα in cell lines.


RESULTS
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.


CONCLUSIONS
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.
Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
Lei
L
Deng
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Hui
H
Yang
Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
Junwei
J
Tang
Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
Zhe
Z
Lin
Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
Aihong
A
Yin
Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
Yun
Y
Gao
Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China.
Xuehao
X
Wang
Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. jiangrq@njmu.edu.cn.|Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, P.R. China. jiangrq@njmu.edu.cn.
Runqiu
R
Jiang
Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China. sunbc@njmu.edu.cn.|Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, P.R. China. sunbc@njmu.edu.cn.
Beicheng
B
Sun
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D064593:Heterografts; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements; D015534:Trans-Activators
D047628:Estrogen Receptor alpha; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases