Effect of hepatitis B virus X in inhibiting the apoptosis of trophoblastic cells and its potential mechanism

Yixia Pan; Yayun Lin; Yan Liu; Fanfan Guo; Wentao Zhang; Guiqin Bai

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Effect of hepatitis B virus X in inhibiting the apoptosis of trophoblastic cells and its potential mechanism

VernacularTitle:HBx蛋白抑制滋养细胞凋亡的作用及机制
Author: Yixia PAN ¹ ; Yayun LIN ² ; Yan LIU ³ ; Fanfan GUO ¹ ; Wentao ZHANG ⁴ ; Guiqin BAI ¹
Author Information

1. Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061
2. Department of Reproductive and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032
3. Institute of Infectious Diseases, 5th Medical Center of Chinese PLA General Hospital, Beijing 100141
4. Department of Obstetrics and Gynecology, Xi’an No. 3 Hospital, Xi’an 710016, China
Publication Type:Journal Article
Keywords: hepatitis B X protein; epidermal growth factor receptor; trophoblast; apoptosis
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(5):674-680
CountryChina
Language:Chinese
Abstract: 【Objective】 To investigate the relationship between hepatitis B virus X （HBx） protein and EGFR promoter， and the role of HBx protein in activating EGFR/PI3K/p-Akt signaling pathway and inhibiting apoptosis. 【Methods】 EGFR promoter plasmids were constructed and the relationship between HBx and EGFR promoters was characterized using a luciferase reporter assay. EGFR-overexpressing trophoblast cells were constructed， and EGFR expression in the overexpressing cells was knocked down using EGFR shRNA. The expression and localization of EGFR/PI3K/p-Akt were detected by Western blotting and confocal laser microscopy. Cell apoptosis was analyzed using flow cytometry. HBV plasmids carrying either full-length HBx or HBx with a deletion mutation （ΔHBx） and HBx plasmids were transfected into two types of trophoblast cells； HBx and PI3K/p-Akt protein expressions were detected by Western blotting. Cell apoptosis was analyzed using flow cytometry. 【Results】 Co-transfection of HBx and EGFR promoter plasmids in JEG-3 and HTR-8/Svneo cells significantly elevated the expression of EGFR promoter driven luciferase compared with the control group （P<0.01）. In EGFR-overexpressing cells， the expression of PI3K/p-Akt was significantly increased （P<0.01）， whereas the apoptosis rate was significantly decreased for JEG-3 cells and HTR-8/Svneo cells （both P<0.01）. These results were reversed in the EGFR-knock down group. When the intracellular HBx protein was expressed in JEG-3 and HTR-8 cells， PI3K/p-Akt protein expression was significantly increased （both P<0.05）， and the proportion of apoptosis was significantly decreased （both P<0.05）. 【Conclusion】 In placental trophoblast cells， HBx protein activates the expression of EGFR by acting on the EGFR promoter， and inhibits the apoptosis of trophoblast cells via the downstream EGFR/PI3K/p-Akt signaling pathway.