The Role Of LPCAT1 In Gastric Cancer

Gastric cancer is one of the top five malignant tumors in the world originating from the epithelium of the gastric mucosa.The early symptoms of gastric cancer are not obvious while the diagnosis is already in the advanced stage of cancer,so the prognostic survival time of gastric cancer is short and the mortality rate is high.Lysophosphatidylcholine transferase 1(LPCAT1)is the key enzyme in the process of membrane lipid remodeling,changing the fluidity of membrane phospholipids and regulating the biological functions of cell membranes.More and more studies have shown that LPCAT1 plays an important role in the occurrence and development of cancer.Therefore,in this study,we propose for the first time that LPCAT1 promotes the occurrence of gastric cancer,and LPCAT1 can be used as a marker for early molecular diagnosis of gastric cancer.This project analyzes the expression levels of LPCAT1 in gastric cancer patients and normal people through online biometric analysis websites GEPIA2,UALCAN(based on TCGA and GTEx databases)and GEO database(GSE19826).The expression of LPCAT1 in gastric cancer tissues and adjacent tissues at the mRNA levels has been detected.Experimental results show that LPCAT1 is highly expressed in cancer patients and tissues,and LPCAT1 is expected to become a marker for early molecular diagnosis of gastric cancer.Through cell proliferation and scratch experiments,we have found that knocking down LPCAT1 significantly inhibited cell proliferation and migration,with inhibiting the expression of the genes related to cell proliferation and migration at the mRNA levels and blocking cell cycle progression in the G0/G1 phase.Knocking down LPCAT1 can promote the ferroptosis which is nonapoptotic pathway.It can Inhibit the expression of GPX4 at protein levels,and then promotes the accumulation of Lipid-ROS which activates the conduction of the p38 MAPK/STAT1 signaling pathway.Finally blocking the cell cycle and inhibiting cell proliferation.Ferrostatin-1 is an effective iron death inhibitor.After Ferrostatin-1 treatment,Lipid-ROS decreases in the cell,and the activation of p38 MAPK/STAT1 is antagonized.It is further verified that knocking down LPCAT1 can block cell cycle progression in G0/G1 phase through ROS/p38 MAPK/STAT1 signaling pathway,and then inhibits the proliferation and migration of gastric cancer cells.Above all,LPCAT1 can be used as a potential target for gastric cancer detection and treatment.