A retrospective study of NENs and miR-224 promotes apoptosis of BON-1 cells by targeting PCSK9 inhibition

// Jian’an Bai 1 , He Na 2 , Xiumei Hua 2 , Yaling Wei 2 , Tian Ye 1 , Yiqiang Zhang 3 , Guo Jian 4 , Weiwen Zeng 2 , Lijun Yan 2 , Qiyun Tang 2 1 Department of Gastroenterology, Sir Run Run Hospital Affiliated with Nanjing Medical University, Nanjing, China 2 Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China 3 Department of Radiology, Linyi People's Hospital, Dezhou, China 4 Department of Orthopaedics, Linyi People’s Hospital, Dezhou, China Correspondence to: Qiyun Tang, email: tqy831@163.com Keywords: NENs, epidemiology, LDL-C, PCSK9, miR-224 Received: February 29, 2016      Accepted: December 16, 2016      Published: December 28, 2016 ABSTRACT Neuroendocrine neoplasms (NENs) represent relatively rare tumors. The lack of diagnostic, therapeutic method and prognostic factors makes them a challenge to us. We retrospectively reviewed the data of 205 NENs patients among which 157 cases were followed-up. Proprotein convertase subtilisin/kexin 9 (PCSK9), a regulator of low density lipoprotein cholesterol (LDL-C), was confirmed as a target gene of microRNA-224. 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). MicroRNA-224 agomir and PCSK9 siRNA could promote apoptosis and suppress proliferation, invasion of BON-1 cells ( P < 0.05), but increase the level of glucocorticoid (GC, P < 0.05). Taken together, age, tumor grading and LDL-C level are independent risk factors of NENs. The miR-224/PCSK9/GC axis binds to tumorigenesis and prognosis of pancreatic NENs (p-NENs).