Preliminary Study On The Role Of PMEPA1 In Gastric Cancer And Its Molecular Mechanism

Gastric cancer is one of the major diseases threatening human life and health.Surgical resection is one of the most effective treatments.However,most patients are already in the middle and advanced stages when they are diagnosed and are not suitable for surgical treatment.In recent years,molecular targeted therapy combined with chemotherapy has been widely used in the treatment of advanced gastric cancer,but there are still problems such as large differences in individual curative effects and drug resistance.Therefore,this project aims to explore the potential molecular mechanisms of gastric cancer and provide potential molecular markers for the early diagnosis and clinical treatment of gastric cancer.This study first conducted mining and analysis of the expression profile data of gastric cancer clinical samples from the GEO database(GSE103236),and found that compared with normal gastric tissue,the expression of 54 genes was up-regulated and the expression of 18 genes was down-regulated(P<0.01).Among them,the expression of Prostate Transmembrane Protein Androgen Induced 1(PMEPA1)was significantly up-regulated(log FC=2.2,P<0.01).We also analyzed the expression of PMEPA1 in gastric cancer samples from the TCGA database and found that the expression of PMEPA1 in gastric cancer tissues was significantly up-regulated(P<0.05).We used real-time fluorescent quantitative PCR to further verify the relative expression of PMEPA1 in 18 gastric cancer clinical samples.Compared with normal gastric tissues,the expression level of PMEPA1 in 8 gastric cancer tissues was significantly up-regulated.The above results can indicate that the expression of PMEPA1 is up-regulated in gastric cancer.In order to study the biological function of PMEPA1 in gastric cancer,we knocked down and overexpressed PMEPA1 in SGC-7901 and MGC-803 gastric cancer cell lines,respectively,and explored the effects of its expression level on the proliferation,migration,invasion,apoptosis and cell proliferation of gastric cancer cells.The impact of the cycle.Experimental results show that knocking down PMEPA1 leads to cell G1 phase arrest and reduces the proliferation ability of gastric cancer cells.After overexpression of PMEPA1,the proportion of cells in G1 phase decreases and promotes cell proliferation.Knockdown of PMEPA1 inhibits the migration and invasion of gastric cancer cells,while overexpression of PMEPA1 has the opposite effect.The apoptosis experiment proved that PMEPA1 has the effect of inhibiting the apoptosis of gastric cancer cells.In short,PMEPA1 can promote the proliferation,migration and invasion of gastric cancer cells,promote the transition of gastric cancer cell cycle G1/S phase,and inhibit cell apoptosis.In addition,this study conducted a preliminary study on the molecular mechanism of PMEPA1 in gastric cancer.The results showed that TGF-β can induce the expression of PMEPA1,and PMEPA1 can inhibit the phosphorylation of Smad2 and Smad3 downstream of the TGF-β signal to antagonize the classic TGF-β signal.It suggests that PMEPA1 may participate in the occurrence and development of gastric cancer through the TGF-β signal pathway.The development of this topic is helpful to clarify the function and potential molecular mechanism of PMEPA1 in gastric cancer,and can provide valuable molecular markers for early diagnosis and clinical treatment of gastric cancer.