Effect Of PRMT2 On The Aerobic Glcolysis Of Breast Cells Through PI3K/Akt/mTOR/HIF-1? Signaling Pathway

ObjectiveTo investigate the effect of protein arginine methyltransferase2(PRMT2)on the aerobic glycolysis of breast cancer cell line MDAMB-231 through PI3K/Akt/mTOR/HIF-1? signaling pathway.MethodsIn vitro,cultured breast cancer cells MDA-MB-231 were studied as the subject.Cells transfected with pcDNA3.1(+)empty vector plasmid were set as the negative control group(NC).Cells transfected with pcDNA3.1(+)-PRMT2 plasmid were set as the PRMT2 high expression group(PRMT2).Then the cells treated with PI3 K inhibitor LY294002(20 ?mol/L),mTOR inhibitor AZD8055(40 ?mol/L)or HIF-1? inhibitor YC-1(50 ?mol/L),respectively.Thus,the experiment was divided into four groups: NC group,NC+inhibitor group,PRMT2 group and PRMT2+inhibitor group.Specific methods are as follows:1.Glucose consumption and lactic acid accumulation of breast cancercells MDA-MB-231 in each group were measured by glucose and lactic acid test kit.2.The protein expression of glycolytic related enzymes of breast cancer cells MDA-MB-231 in each group were detected by western blotting.3.The migration and invasion ability of breast cancer cells MDAMB-231 in each group were detected by cell scratch and Traswell experiments.Results1.The results of glucose and lactic acid test showed that the glucose uptake and lactic acid accumulation increased in the PRMT2 high expression group compared with the NC group(P<0.01);treatment with LY294002 after high expression of PRMT2,the glucose uptake and lactic acid accumulation were significantly reduced compared with the PRMT2 high expression group(P<0.01);treatment with AZD8055 after high expression of PRMT2,the glucose uptake and lactic acid accumulation were significantly reduced compared with the PRMT2 high expression group(P<0.01);treatment with YC-1 after high expression of PRMT2,the glucose uptake and lactic acid accumulation were also significantly reduced compared with the PRMT2 high expression group(P <0.01).2.Western blot results showed that the expression of most glycolyticrelated enzyme such as HK2,PKM2 increased in the PRMT2 high expression group compared with the NC group(P<0.05);treatment with LY294002 after high expression of PRMT2,the protein expression of pAkt,p-mTOR and glycolytic related enzyme such as HK2,PFKP,PKM2 decreased compared with the PRMT2 high expression group(P<0.05);treatment with AZD8055 after high expression of PRMT2,the protein expression of p-mTOR and glycolytic related enzyme such as HK2,PKM2,LDHA decreased compared with the PRMT2 high expression group(P<0.05);treatment with YC-1 after high expression of PRMT2,the protein expression of glycolytic related enzyme such as HK2,PKM2 decreased compared with the PRMT2 high expression group(P <0.05).3.Cell scratch and Transwell experiments showed that the cell migration and invasion ability of the PRMT2 high expression group were enhanced compared with the NC group(P<0.05);treatment with LY294002 after high expression of PRMT2,the ability of cell migration and invasion decreased compared with the PRMT2 high expression group(P<0.01);treatment with AZD8055 after high expression of PRMT2,the ability of cell migration and invasion decreased compared with the PRMT2 high expression group(P<0.01);treatment with YC-1 after high expression of PRMT2,the ability of cell migration and invasion decreased compared with the PRMT2 highexpression group(P<0.01).Conclusions1.PRMT2 upregulates glycolysis-related enzyme expression through PI3K/Akt/mTOR/HIF-1? signaling pathways,thus promoting aerobic glycolysis metabolism in breast cancer cell line MDA-MB-231.2.PRMT2 enhances migration and invasion ability of breast cancer cell line MDA-MB-231 through PI3K/Akt/mTOR/HIF-1?signaling pathways.