Effect and potential molecular mechanism of FOXA2 on cell proliferation, migration and invasion of hepatocellular carcinoma
10.3760/cma.j.cn113884-20210307-00088
- VernacularTitle:叉头框蛋白A2表达对肝癌细胞增殖、迁移和侵袭的影响及潜在机制
- Author:
Zhongshan LU
1
;
Xiaoyan HU
;
Wei WANG
;
Qifa YE
;
Guizhu PENG
Author Information
1. 武汉大学中南医院 武汉大学肝胆疾病研究院 武汉大学移植医学中心 移植医学技术湖北省重点实验室，武汉 430071
- Keywords:
Carcinoma, hepatocellular;
Forkhead box protein A2;
Hypoxia inducible factor-1α;
Proliferation;
Migration;
Invasion
- From:
Chinese Journal of Hepatobiliary Surgery
2021;27(9):694-698
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of forkhead box protein A2(FOXA2) on cell proliferation, migration and invasion of hepatocellular carcinoma and the potential molecular mechanism.Methods:From January 2019 to December 2020, 10 cases of hepatocellular carcinoma patients from Zhongnan Hospital of Wuhan University were collected for study, including 7 males and 3 females, with an average age of 53 years. FOXA2 expression was detected in human liver cancer cell line, and the highest expression of FOXA2 was found in HepG2 cells transfected with FOXA2 overexpression plasmid. Immunohistochemistry and qRT-PCR were used to detect the expression of FOXA2. Western blot was used to detect the expression of FOXA2, hypoxia-inducible factor-1 α (HIF-1α), vascular endothelial growth factor A (VEGFA), B-cell lymphofactor-2 (Bcl-2), matrix metalloproteinase (MMP) 7, and glucose transporter (GLUT) 1. EdU assay was used to study cell proliferation, and Transwell chamber assay was used to study cell migration and invasion.Results:The relative expression of FOXA2 in liver cancer tissues were lower than those in adjacent tissues both at mRNA and protein levels, with statistical significance (both P<0.05). FOXA2 overexpression group showed lower cell proliferation rate (30.0±3.2)%, migration rate (10.6±1.1), and invasion rate (12.8±0.8) comparing with negative control group (67.0±3.6)%, (81.0±5.4), (74.8±4.5). The difference was statistically significant (all P<0.05). Expression of HIF-1α and its downstream targets VEGFA, MMP7, GLUT1 and Bcl-2 was decreased after over-expression of FOXA2 in HepG2 cells. Conclusion:FOXA2 inhibits proliferation, migration, and invasion in hepatocellular carcinoma by regulating HIF-1α signaling pathway, suggesting that FOXA2 is a potential target for the treatment of hepatocellular carcinoma.
