Mechanism of immune escape induced by ZBED2 induced PD-L1 expression in hepatocellular carcinoma through glycolysis metabolism
10.3969/j.issn.1000-484X.2025.02.018
- VernacularTitle:ZBED2通过糖酵解代谢诱导肝细胞癌中PD-L1表达促进免疫逃逸的机制研究
- Author:
Jinshi HUANG
1
;
Yating DING
1
;
Jianzhong CAO
1
Author Information
1. 南通大学附属医院药学部,南通 226000
- Publication Type:Journal Article
- Keywords:
ZBED2;
Glycolysis;
Hepatocellular carcinoma;
Immune escape
- From:
Chinese Journal of Immunology
2025;41(2):367-373
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of zine finger BED domain-containing protein 2(ZBED2)on immune escape of hepatocellular carcinoma(HCC)through glycolysis pathway and its potential mechanism.Methods:Expression of ZBED2 in HCC tis-sues and binding sites of them were analyzed in bioinformatics database,the pathway regulated by ZBED2 was analyzed,as well as the correlation between ZBED2 and glycolysis genes.qPCR and Western blot were used to detected expressions of ZBED2 and pro-grammed death-ligand 1(PD-L1)in HCC cells,cell viability was detected by MTT,toxicity of CD8+T cells was detected by cytotoxicity assay,and cytokine expression was detected by ELISA.Extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)were detected by extracellular flow analyzer,glycolytic gene expression was detected by qPCR,and glycolytic index was detected by kit.Expression of CD8+T cell in tumor tissues was detected by immunohistochemical staining.Results:ZBED2 was up-regulated in HCC,overexpression of ZBED2 could promote expression of PD-L1,while inhibit cytotoxicity of CD8+T cells to HCC.Overexpression of ZBED2 inhibited CD8+T cell activity in HCC by activating glycolysis pathway,and further addition of glycolysis inhibitor 2-DG at-tenuated the above results.In vivo experiments showed that ZBED2 knockdown inhibited tumor growth,inhibited PD-L1 expression,while promoted CD8+T cell infiltration in vivo.Conclusion:ZBED2 induces expression of PD-L1 in HCC through glycolytic metabo-lism,and promotes immune escape.
