Inhibitory effect of MEGL gene on glioblastoma cells and its mechanism
10.13200/j.cnki.cjb.004439
- VernacularTitle:MEGL基因对胶质母细胞瘤细胞的抑制作用及其机制
- Author:
LI Yuyu
- Publication Type:Journal Article
- Keywords:
Methionine(Met);
Methionine-γ-lyase(METase);
Glioblastoma(GBM);
MAPK signaling pathway
- From:
Chinese Journal of Biologicals
2025;38(03):285-290
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effect of methionine-γ-lyase(METase) gene MEGL on glioblastoma(GBM) cells and its potential molecular mechanism,and to provide new ideas for the development of MEGL drugs.Methods MEGL expression system mediated by lentivirus was constructed and used to infect human GBM cell lines U87 and snb19,and the cells infected with empty virus were as the control.RT-qPCR and Western blot were used to detect the expression of MEGL gene and protein.The levels of methionine(Met) and its metabolites were detected by liquid chromatography tandem mass spectrometry(LC-MS/MS).The cell proliferation was measured by cell counting method.The changes of cell cycle were detected by flow cytometry,and the expression of cell cycle-related proteins(CDK2,CDK4 and p21) and mitogen-activated protein kinase(MAPK) signaling pathway proteins was determined by Western blot.Results Met levels in U87 and snb19cells stably expressing MEGL gene decreased significantly(t=10.996 and 15.733,respectively,each P <0.001).Furthermore,MEGL significantly suppressed the proliferation of U87(on the 3rd,4th and 5th day,t=14.698,9.746,and 12.263,respectively,each P<0.001) and snb19 cells(on the 3rd,4th and 5th day,t=8.480,6.939,and 13.258,respectively,each P <0.001),inducing a notable increase in the proportion of G0/G1 phase(t=7.997,P P<0.001).MGEL gene decreased the expression of cell cycle related proteins CDK2 and CDK4(t=8.471 and 3.369,P=0.0011 and 0.0281,respectively),while promoting the expression of p21(t=10.761,P <0.001).Moreover,it significantly inhibited the expression of proteins related to the MAPK signaling pathway,including p-p38,p-ERK1/2,and p-JNK(t=3.401,6.493,and9.413,P=0.027 2,0.002 9,and <0.001,respectively).Conclusion The MEGL gene can significantly reduce the intracellular Met levels in U87 and snb19 cells,while also inhibiting cell proliferation and cell cycle progression.This inhibitory effect may be achieved through MAPK signaling pathway.
