Apoptosis,inhibits proliferation,and migration of gastric cancer cells HGC27 via MAPK pathway by the knockdown of A-type nuclear lamins gene
Objective To explore the effect of knocking down A-type nuclear laminins gene(LMNA)on the proliferation,migration,and apoptosis of human gastric cancer cells HGC27 and its possible mechanism.Methods The expression of LMNA gene in normal gastric tissues and gastric cancer tissues was analyzed by bioinformatics.Human gastric cancer cells HGC27 at logarithmic growth stage were divided into 4 groups,which include LMNA knockdown group(si-1,si-2,si-3)and control group(si-NC group)according to whether LMNA gene was knocked down.The si-2 group with the highest transient transfection rate was used as the si-LMNA group.CCK-8 assay was used to detect cell viability.Transwell and scratch assay were used to detect the invasion and migration ability of cells.Flow cytometry was used to detect apoptosis and cell cycle.Western blot was used to detect the expressions of apoptosis-related proteins Bax,Caspase3,Bcl-2,and p38,p-p38,ERK1/2,and pERK1/2 in mitogen-activated protein kinase(MAPK)pathway.Chicoric acid,a specific activator of MAPK pathway,was added to si-LMNA group to further verify the expression of LMNA.Results The results of bioinformatics analysis suggested that the expression of LMNA gene was high in gastric cancer tissues,and the survival rate of patients with low expression of LMNA was higher.Compared with the si-NC group,the cell viability of si-LMNA group decreased(P＜0.05),the expressions of apoptotic proteins Bax and Caspase3 increased,the anti-apoptotic protein Bcl-2 decreased,and the apoptosis rate increased(P＜0.05).The cell cycle was blocked in G0/G1 phase,the number of cells in S phase decreased(P＜0.05),invasion and migration ability decreased(P＜0.05),and the phosphorylation levels of p38 and ERK1/2 decreased(P＜0.05).The expression of LaminA/C and phosphorylation levels of p38 and ERK1/2 increased after the addition of the activator.The expression of apoptosis-related proteins was reversed and the invasion and migration ability was promoted(P＜0.05).Conclusion Knockdown of LMNA gene can facilitate the apoptosis of gastric cancer cells,block the cell cycle in G0/G1 phase,and inhibit the proliferation,invasion,and migration of gastric cancer cells.The mechanism may be closely related to MAPK signaling pathway.
A-type nuclear lamins genecellgastric cancermitogen-activated protein kinase signaling pathwayproliferationmigration
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