LncRNA TMPO-AS1 Serves As A Competitive Endogenous RNA To Regulate The Autophagy Of Pancreatic Cancer By Regulating MiR-873-3p/TRIM11 Axis

Objective:Pancreatic cancer is a malignant stage with high levels of malignancy,diagnosis and treatment,and about 90%of ductal adenocarcinoma originating from the ductal epithelium.The morbidity and mortality rate have increased significantly in recent years.Its 5-year survival rate less than 1%,and which is one of the worst prognosis of malignant tumors.More and more studies have found that long non coding RNA(lncrna)plays a significant role in the progress of pancreatic cancer(PC).Tmpo antisense RNA 1(tmpo-asl)has been found to play a role in a variety of tumors in recent years,but its role in PC remains unclear.Method:RT-PCR was used to detect the expression of tmpo-as1 in PC tissues,and the correlation between tmpo-asl expression level and clinical data and prognosis was analyzed.In vitro,knockdown and overexpression experiments were conducted to verify the effects of tmpo-as1 on proliferation,migration and epithelial mesenchymal transition(EMT)of PC-3 and PANC-1.In addition,the downstream molecular targets of tmpo-as1 were analyzed by bioinformatics.The relationship between tmpo-asl and mir-873-3p,mir-873-3p and trimll was verified by double luciferase assay and RNA immunoprecipitation(RIP)experiment.The protein expression of trim 11 and Akt was detected by Western blotResults:Tmpo-asl was significantly up-regulated in PC tissues and was closely related to tumor volume and poor prognosis of PC.Overexpression of tmpo-asl significantly promoted the proliferation,migration and EMT of PC-3 cells,while knockdown of tmpo-asl inhibited the proliferation,migration and EMT of PANC-1 cells.In addition,mir-873-3p is the target of tmpo-asl.Overexpression of mir-873-3p inhibited the progression of PC and weakened the tumor promoting effect of tmpo-as1.Further studies confirmed that mir-873-3p targeted the 3’untranslated region(3’UTR)oftrimp11.Knockdown of trimp11 inhibited the proliferation,migration and invasion of PC,and weakened the activation of Akt.Further study on the downstream mechanism of trim 11 showed that knockdown of trim11 could reduce the proliferation,invasion and migration of PC by inhibiting autophagyConclusion:tsmpo-as1 regulates PC autophagy by regulating mir-873-3p/trim11 axis,thus promoting PC proliferation,migration and EMT.