TRIM15 Promotes The Invasion And Metastasis Of Pancreatic Cancer Through The Ubiquitination Of APOA1

ObjectiveOne of the main reasons for the high mortality of pancreatic cancer is the loss of the best chance of surgical treatment at the first discovery,which primarily due to the high probability of invasion and metastasis of pancreatic cancer.In this study,we find TRIM15 is associated with malignant biological properties in pancreatic cancer.We aim to investigate the core mechanism of TRIM15 in promoting EMT by downregulating APOA1 in pancreatic cancer,and intend to provide a new idea and theoretical basis for the diagnosis of pancreatic cancer.MethodsThe effect of TRIM15 on prognosis of pancreatic cancer was analyzed by bioinformatics.IHC assay and Western Blotting were used to measure the expression of TRIM15 in pancreatic cancer tissues and cell lines.Short hairpin RNA(sh RNA)or overexpression plasmid of TRIM15 and APOA1 were transfected into pancreatic cancer cell lines in order to explore their biological functions both in vitro and in vivo.The ability of cells to invade and migrate were evaluated by transwell and wound healing.RT-q PCR,Western Blotting and immunofluorescence assay were used to detect the expression of molecules related to EMT.Bio-mass spectrometry was used to search for polypeptides interact with TRIM15.The interaction between APOA1 and ubiquitin was verified by immunoprecipitation assay.The ability of distant metastasis of pancreatic cancer was examined in nude mice model.ResultsTRIM15 is highly expressed in pancreatic cancer and associated with poor prognosis.While TRIM15 promotes the invasive and migratory abilities of pancreatic cancer,APOA1,which is negatively correlated with TRIM15,inhibits the malignant progression.It is proved by experiments that TRIM15 promotes the degradation of APOA1 protein by ubiquitination.So that inhibits the negative regulation of APOA1 on the progression of pancreatic cancer and facilitates EMT.Tail vein injection model of nude mice verify the promotional role of TRIM15 in distant metastasis of pancreatic cancer.ConclusionTRIM15 is associated with poor prognosis of pancreatic cancer.It hydrolyzes APOA1 protein through the ubiquitin-proteasome system to inhibit its negative regulatory effects on pancreatic cancer,thus promoting cancer progression by stimulating EMT and increasing the ability of distant metastasis of pancreatic cancer.