Experimental Study on the Mechanism of Mitochondrial Autophagy Promoted DLBCL Progression Mediated by PLA2G4C Via p38/MAPK Signaling Pathway
10.3969/j.issn.1671-7414.2024.06.010
- VernacularTitle:PLA2G4C通过p38/MAPK信号通路介导线粒体自噬促进DLBCL进展的实验研究
- Author:
Jingru WANG
1
;
Lin ZHANG
;
Fengmin LI
Author Information
1. 秦皇岛市第一医院血液内科,河北 秦皇岛 066000
- Keywords:
diffuse large B-cell lymphoma;
phospholipase A2 group Ⅳ C;
mitochondrial autophagy;
p38/MAPK signal path
- From:
Journal of Modern Laboratory Medicine
2024;39(6):61-66
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of phospholipase A2 Group Ⅳ C(PLA2G4C)in diffuse large B-cell lymphoma(DLBCL)and its possible regulatory mechanism.Methods The protein expression of PLA2G4C in DLBCL tissues and cells was detected by Western blot.DLBCL cell lines with PLA2G4C overexpression or knockdown expression were constructed,and the cells were treated with autophagy inhibitor Chloroquine(CQ)or p38 inhibitor SB203580 for 24 h.Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the transfection efficiency of PLA2G4C;Western blot analysis was performed to detect the expression levels of PLA2G4C protein,mitochondrial autophagy related protein[microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ(LC3 Ⅱ/Ⅰ),Beclin1,p62,PTEN induced putative kinase 1(PINK1)and Parkin]and p38/mitogen activated protein kinases(MAPK)pathway-related protein[Phosphorylated p38/MAPK(p-p38/MAPK)];Cell proliferation,invasion and apoptosis were detected with CCK8,Transwell assay and the flow cytometry,respectively.The effects of PLA2G4C on tumor growth and mitochondrial autophagy in nude mice were further established.Results The PLA2G4C protein expression in lymphoma tissues of DLBCL patients was significantly higher than that in lymph nodes with reactive hyperplasia(3.47±0.42 vs 1.01±0.02),and the difference was statistically significant(t=-37.002,P<0.001).The PLA2G4C protein level in DLBCL cells was significantly higher than that in human lymphoblast-like cell lines and B-cell lymphoma cell lines,and the difference was statistically significant(F=73.771,P<0.001).Silencing PLA2G4C significantly decreased the viability and invasion ability of DLBCL cells,and induced apoptosis,with statistical significance(t=6.909～11.390),Overexpression of PLA2G4C gave the opposite result(t=2.392～19.778),and the differences were statistically significant(all P<0.001).PLA2G4C overexpression significantly promoted the occurrence of mitochondrial autophagy,while CQ or SB203580 treatment could significantly reverse the effects of PLA2G4C overexpression on the biological behavior of DLBCL cells and mitochondrial autophagy.In vivo nude mice experiments showed that PLA2G4C knockdown significantly inhibited tumor growth and mitochondrial autophagy related protein expression in transplanted nude mice,and the differences were statistically significant(t=13.816～25.926,all P<0.001).Conclusion PLA2G4C is up-regulated in DLBCL,which may promote tumor cell proliferation and invasion,inhibit cell apoptosis,and participate in the occurrence and development of DLBCL by promoting mitochondrial autophagy mediated by p38/MAPK signaling pathway.
