The Experssion And Its Clinical Significance Of Sterol O-acyltransferase 1(SOAT1) In Gastric Cancer

Objective:To investigate the expression of sterol o-acyltransferase 1(SOAT1)in gastric cancer and its clinical significance.Methods:(1)Tumor tissue and paired para-cancer tissue samples from operable gastric cancer patients were collected and the expression of SOAT1 was tested by immunohistochemical(IHC)technique.Then the relationship between SOAT1 and clinicopathological data was analyzed.(2)The total proteins of normal gastric epithelial cells(GES-1)and gastric cancer cells(MKN45,N87,HGC-27,AGS,and SUN-1)were extracted and the expression of SOAT-1 in gastric cancer cells and normal gastric epithelial cells was detected by Western blot.(3)SOAT1-short hairpin RNA(shRNA)interference or-overexpression lentiviral vector and their controls were prepared.(4)MKN45 gastric cancer cells were selected to establish SOAT1-knockdown(MKN45-shSOAT1)or-overexpression(MKN45-SOAT1)stable gastric cancer cell lines and their controls(MKN45-shcontrol or MKN45-mock),and the transfection efficiency of the cells was detected by fluorescence inverted microscope and flow cytometry;Western blot and reverse transcription-quantitative polymerse chain reaction(RT-qPCR)were used to identify the efficiency of SOAT1 knockdown and overexpression.(5)The effects of SOAT1 on the growth,proliferation,colony formation,migration and invasion of gastric cancer cells were analyzed by cell functional experiments such as cell counting kit-8(CCK-8)assay,scratch assay,plate cloning assay,and Transwell migration and invasion assays.(6)SOAT1-associated signaling pathways in gastric cancer were analyzed based on Kyoto Encyclopedia of Genes and Genomics(KEGG)database enrichment.The effect of SOAT1 on phosphoinositide 3-kinase-protein kinase B(PI3K-AKT)was validated by Western blot.Results:(1)The expression level of SOAT1 in gastric cancer tissues was significantly higher than that in para-cancer tissues.Its level was positively correlated with tumor size and Tumor Node Metastasis(TNM)staging but negatively correlated with differentiation.(2)Compared with normal gastric epithelial cells,the expression level of SOAT1 in gastric cancer cells was significantly up-regulated.(3)SOAT 1-knockdown gastric cancer cell line MKN45-shSOATl and its control MKN45-shcontrol,as well as SO AT 1-overexpression gastric cancer cell line MKN45-SOAT1 and its control MKN45-mock were successfully established.(4)Overexpression of SOAT1 could significantly promote the growth,proliferation,colony formation,migration and invasion of gastric cancer cells,whereas its knockdown produced an opposite effect in gastric cancer cells.(5)KEGG enrichment analysis and Western blot result showed that the elevated expression of SOAT1 was associated with the activation of PI3K-AKT signaling pathway in gastric cancer.Conclusion:SOAT1 is up-regulated in gastric cancer,which is associated with malignant clinicopathological features of gastric cancer patients.SOAT1 can promote the proliferation and metastasis of gastric cancer cells,and facilitated the activation of PI3K-AKT signaling pathway in gastric cancer cells.