Effects Of EMP1 Gene Silencing On The Biology Of Pancreatic Cancer Cells And Its Mechanism

Objective: To explore the biological role and cancer-promoting mechanism of EMP1 in pancreatic cancer cells.To elucidate the differential expression of EMP1 in human pancreatic cancer cells and its effects on the biological behavior of pancreatic cancer As PC-1 and Bx PC-3 cells and their downstream molecular mechanisms,which will provide theoretical basis for pancreatic cancer patients in prognostic assessment and molecular targeting therapy.Methods: Firstly,the expression of EMP1 in pancreatic cancer tissues and its relationship with clinical prognosis were analyzed in TCGA and GTEx databases,and the signaling pathways of pancreatic cancer progression that EMP1 may be involved in regulating were explored by GEO analysis of EMP1 co-expressed genes and KEGG pathway enrichment analysis.Next,pancreatic cancer cell lines were cultured,and the expression differences of EMP1 m RNA and protein levels were detected by RT-PCR and WB.Lentiviral vectors were constructed and transfected with pancreatic cancer As PC-1 and Bx PC-3 cell lines to obtain knockdown experimental groups(EMP1-sh1,EMP1-sh2,EMP1-sh3),and negative control group(Negative control)was transfected with blank vector virus.CCK8,clone formation,scratch and Transwell assays were used to detect the effects of down-regulation of EMP1 on the biological behavior of pancreatic cancer cells,and WB was used to detect the effects of down-regulation of EMP1 on proliferation,apoptosis and downstream related molecular signaling pathway proteins of pancreatic cancer cells.Results: 1.High expression of EMP1 in cancerous tissues and cells compared to normal pancreatic tissues and cells has clinical diagnostic implications for pancreatic cancer patients.High expression of EMP1 is an independent risk factor for prognosis of pancreatic cancer patients and is closely associated with poor prognosis and is a potential prognostic biomarker.The GEO results showed that EMP1 is involved in multiple biological processes and molecular functions.enrichment of the KEGG pathway.The results showed that EMP1 affects pancreatic cancer progression through multiple signaling pathways including PI3K-AKT.2.EMP1 m RNA and protein were highly expressed in pancreatic cancer cell lines compared to normal pancreatic epithelial cells(P < 0.05).Downregulation of EMP1 expression significantly inhibited the proliferation,invasion and migration ability of As PC-1 and Bx PC-3 cells(P <0.05).3.KEGG enrichment analysis showed that most of the genes were enriched in the PI3K-AKT pathway.Downregulation of EMP1 in pancreatic cancer cell lines significantly reduced P-PI3 K,P-AKT protein expression.Compared with the Negative control group,knockdown of EMP1 decreased apoptotic protein expression in cancer cells,increased Bax protein expression,and decreased Bcl-2/Bax ratio.Conclusions: High expression of EMP1 in pancreatic cancer tissue cells has a certain value for the diagnosis and prognosis of pancreatic cancer,and high expression of EMP1 is associated with poor patient prognosis.The mechanism may be that EMP1 promotes the proliferation,invasion,and migration of cancer cells through PI3K-AKT pathway,and inhibits apoptosis of cancer cells.Therefore,EMP1 plays a supportive role for tumor growth in pancreatic cancer and may be a potential target for diagnosis,treatment and prognosis of pancreatic cancer.