A Retrospective Study Of NENs And MiR-224 Promotes Apoptosis Of BON-1 Cells By Targeting PCSK9 Inhibition

Background and Purposes: Neuroendocrine neoplasms(NENs)represent relatively rare tumors.The lack of diagnostic,therapeutic method and prognostic factors makes them a challenge to us.This study aimed to analyze the factors that influence the prognosis of patients with NENs and search new therapeutic targets for NENs.Methods: We retrospectively reviewed the data of 205 NENs patients among which 157 cases were followed-up.The clinical features and prognostic factors of patients with NENs were analyzed for survival analysis.Using mi RNA Target-Scan,we found that PCSK9 is a target of mi R-224 and confirmed using a luciferase reporter gene.Up-regulate or down-regulate the expression of PCSK9 in p-NENs cells(BON-1)by transfection with mi R-224 agomir or PCSK si RNA.Western blot and q RT-PCR were used to analyze the effect of mi R-224 on the expression of PCSK9 RNA and protein.We detected GC level by ELISA and the effect of mi R-224 and PCSK9 on BON-1 cell apoptosis,migration and invasion by TUNEL and Tranwell assays.Results: We found an increased incidence of NENs from 2012 to 2015.Women were usually diagnosed at earlier stages than men(P < 0.05).Tumor grading was associated with primary tumor site,especially esophagus and cardia NENs all at G3(P <0.001).Age,tumor grading and LDL-C levels were independent risk factors of digestive NENs.Low LDL-C level was significantly correlated with survival rate and median overall survival(OS,P< 0.05).Micro RNA-224 agomir and PCSK9 si RNA could promote apoptosis and suppress proliferation,invasion of BON-1 cells(P < 0.05),but increase the level of glucocorticoid(P < 0.05).Conclusions: Taken together,age,tumor grading and LDL-C level are independent risk factors of NENs.The mi R-224/PCSK9/GC axis binds to tumorigenesis and prognosis of pancreatic NENs(p-NENs).