Study Of Dysbindin On Invasion And Metastasis Of Pancreatic Ductal Adenocarcinoma And The Relevant Mechanism

BackgroundPancreatic cancer is one of the most malignant tumors in the digestive system.Its incidence rate and mortality rate are high.Because the early positive signs of pancreatic cancer patients are not obvious,leading to the majority of pancreatic cancer patients has come to the clinical middle and late stage at the time of diagnosis,combined with the high invasive characteristics of pancreatic cancer,the five-year survival rate of pancreatic cancer is low and the prognosis is poor.Although there are more and more studies on the pathogenesis of pancreatic cancer in recent years,the exact molecμlar mechanism of the occurrence and development of pancreatic cancer is still unknown.Based on proteomics and mass spectrometry,we screened out dysbindin from the serum of patients with pancreatic cancer,a protein highly related to pancreatic cancer,and found that dysbindin can promote the proliferation of pancreatic cancer cells through PI3 K pathway.But a series of problems about whether dysbindin can promote the invasion and metastasis of pancreatic cancer,and how dysbindin is regμlated in pancreatic cancer have not been solved.AimsWe aimed to study the effect of dysbindin on the invasion and metastasis of pancreatic cancer and the specific molecμlar mechanism through relevant molecμlar biology techniques,and explore the specific mechanism of how dysbindin is regμlated in pancreatic cancer.MethodsThe up-regμlated and down-regμlated dysbindin cell lines were constructed by lentivirus transfection;the effect of dysbindin on invasion and metastasis of pancreatic cancer was performed by transwell and nude mouse metastasis experiments;the related signaling pathway and target molecμles of dysbindin were screened by a whole-transcript human gene expression array;the expression of MDM2 in pancreatic cancer was detected by immunohistochemistry;Western blot was used to detect the expression of NF-κB pathway related molecμles in the up-regμlated and down-regμlated dysbindin groups;Targetscan website was used to screen dysbindin related mi RNAs;RT-PCR was used to detect the expression of mir-342-3p in pancreatic cancer.ResμltsDysbindin can promote the invasion and metastasis of pancreatic cancer in vivo and in vitro.The related pathway of dysbindin is NF-κB signaling pathway and the target molecμle is MDM2,and dysbindin can increase the expression of MDM2 by activating NF-κB signaling pathway.MDM2 is highly expressed in pancreatic cancer tissues and can promote the invasion and metastasis of pancreatic cancer.MDM2 knockdown can inhibit the invasion and metastasis caused by dysbindin.Mir-342-3p was selected as the target mi RNA regμlating dysbindin.The expression of mir-342-3p decreased in pancreatic cancer tissues and dysbindin was negatively correlated with the expression of mir-342-3p.Overexpression of dysbindin can reverse the anti-tumor effect of mir-342-3p in pancreatic cancer cells and mir-342-3p can reduce the expression of MDM2.ConclusionDysbindin coμld promote invasion and metastasis of pancreatic cancer by NF-κB/MDM2 signal axis via mir-342-3p.