Downregulation Of MT2A Promotes The Development Of Pancreatic Cancer Via Interacting With P53

Objective: Pancreatic cancer(PC),one of the most malignant tumors in the world,with a5-year survival rate of less than 5% and had a strong ability of invasion,migration and proliferation.Its occurrence and development process was complex and the relevant mechanism had not been studied thoroughly until now.Therefore,it was of great significance to explore new molecular biomarkers influence of the biological behavior of PC and inhibited its malignant progress.The purpose of this study was to discuss the effect of metallothionein 2A(MT2A)on the biological function of PC by regulating tumor related gene p53.Methods: In tissue level: Immunohistochemistry(IHC),western blotting(WB)and qRT-PCR detection of MT2A expression in PC and its clinicopathological significance.In cell level: The wild-type p53 PC cells(SW1990 and Capan-2)and mutant p53 PC cell Miapaca-2 were selected and transfected with MT2A and p53 si RNA.MT2A silencing cell lines were constructed by transfection,and its effect on the expression of tumor related gene protein was detected by western blotting.The influence of MT2A on the biological behavior of PC cells and its related mechanisms were detected by Transwell cells invasion experiment in vitro,cell MTT test and chemotherapy drug intervention.Results: In tissue level: 1.The expression of MT2A in PC was lower than that in paired normal pancreatic tissue.In 54 pairs of matched PC and paracancerous tissues,MT2A expression was significantly higher in the paracancerous tissues than that in PC tissues(P=0.024)detected by immunohistochemistry.In 16 paired tissue protein samples,MT2A expression in the paracancerous tissues was significantly higher than matched PC tissues detected by western bloting(P<0.01).In 40 paired PC and paracancerous tissues,MT2A m RNA expression in the paracancerous tissues was higher than PC tissues detected by real-time quantitative PCR(P=0.046).There was no correlation between MT2A and mutant p53.2.MT2A expression was negatively correlated with tumor size(P=0.019)and T stage(P=0.006).In cell level: 1.MT2A silencing down-regulated wild-type p53 protein expression,while wild-type p53 silencing also down-regulated of MT2A expression.There was no correlation between MT2A and mutant p53.2.MT2A silencing enhanced the ability of invasion and migration in PC in vitro,while MT2A over-expression resulted in the opposite.The PC cells were treated with si RNA and overexpression plasmids,which were verified by the Transwell cells invasion experiment in vitro.3.MT2A silencing increased the ability of proliferation and decreased the chemosensitivity in PC cells and the reverse was found after over-expression of MT2A in vitro.Conclusion: In this study,MT2A was closely related to the clinicopathological parameters and prognosis of patients with pancreatic cancer.MT2A high expression patients had better overall survival as well as clinicopathological parameters.MT2A silencing in PC cells leads to increased invasion and migration ability in vitro,increased cell proliferation ability and decreased chemosensitivity of pancreatic cancer cells,MT2A overexpression results are the opposite.MT2A interactions with wild-type p53 exist at the protein level in pancreatic cancer cells MT2A may directly or indirectly affect malignant tumor function in pancreatic cancer cells by interacting with p53.