GATA binding protein 4 promotes the expression and transcription of hepatitis B virus by facilitating hepatocyte nuclear factor 4 alpha in vitro

Xiaoqin Lv,Guoqi Lai,Yue Wu,Yang Liu,Ruqing Xu,Qin Xiang,Xia Xiang

doi:10.1186/s12985-021-01668-z

Abstract

BackgroundGATA binding protein 4 (GATA4) has been reported as a potential target of gene therapy for hepatocellular carcinoma (HCC). It is well known that the main cause of HCC is the chronic infection of hepatitis B virus (HBV). However, whether the effect of GATA4 on HBV has not yet been reported.MethodsIn this study, the regulation of GATA4 on HBV was analyzed in vitro. In turn, the effect of HBV on GATA4 was also observed in vitro, in vivo, and clinical HCC patients. Subsequently, we analyzed whether the effect of GATA4 on HBV was related to hepatocyte nuclear factor 4 alpha (HNF4α) in vitro.ResultsThe results showed that GATA4 significantly promoted the secretion of HBV surface antigen (HBsAg) and HBV e antigen in the cell culture medium, improved the replication of HBV genomic DNA, and increased the level of HBV 3.5 kb pre-genomic RNA and HBV total RNA (P < 0.05). Moreover, it was showed that HBV had no significant effect on GATA4 in vitro and in vivo (P > 0.05). At the same time, GATA4 expression was decreased in 78.9% (15/19) of HCC patients regardless of the HBV and HBsAg status. Among them, there were 76.9% (10/13) in HBV-associated patients with HCC (HBV-HCC), and 83.3% (5/6) in non-HBV-HCC patients. In addition, the expression of HNF4α was also up-regulated or down-regulated accordingly when stimulating or interfering with the expression of GATA4. Furthermore, stimulating the expression of HNF4α could only alleviate the HBsAg level and HBV transcription levels, but had no significant effect on GATA4.ConclusionsIn summary, this study found that GATA4 has a positive effect on HBV, and the potential pathway may be related to another transcription factor HNF4α that regulates HBV.

Highlights

It is reported that the global incidence and mortality of hepatocellular carcinoma (HCC) in 2018 are 4.7% and 8.2% respectively, which is the sixth most commonLv et al Virol J (2021) 18:196 factor that regulates cell differentiation and tissue development [4, 5]
Expression of GATA binding protein 4 (GATA4) in cells We first verified the expression of GATA4 in different normal liver cell lines or HCC cell lines via RT-PCR and western blotting (WB) to determine the appropriate cell models
In this study, plasmid adGATA4 was treated in L02 cells and SMMC7721 cells, and GATA4 small interfering RNA (siGATA4) was interfered in HepG2 cells and HepG2.2.15 cells

Summary

Introduction

It is reported that the global incidence and mortality of hepatocellular carcinoma (HCC) in 2018 are 4.7% and 8.2% respectively, which is the sixth most commonLv et al Virol J (2021) 18:196 factor that regulates cell differentiation and tissue development [4, 5]. It is reported that the global incidence and mortality of hepatocellular carcinoma (HCC) in 2018 are 4.7% and 8.2% respectively, which is the sixth most common. Chronic hepatitis B (CHB) is the most common pathogenic factor leading to HCC [14,15,16]. HBV chronic infection accounts for at least 50% of HCC patients in the worldwide [14], and even more than to 90% in some regions [17]. Transcription factors play an important role in chronic HBV infection [18]. GATA binding protein 4 (GATA4) has been reported as a potential target of gene therapy for hepatocellular carcinoma (HCC). It is well known that the main cause of HCC is the chronic infection of hepatitis B virus (HBV). Whether the effect of GATA4 on HBV has not yet been reported

Methods

Results

Conclusion