title: A retrospective study of NENs and miR-224 promotes apoptosis of BON-1 cells by targeting PCSK9 inhibition.
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).
authors.affiliation: Department of Gastroenterology, Sir Run Run Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Jian'an
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: He
authors.initials: H
authors.lastname: Na
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Hua
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology, Sir Run Run Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Radiology, Linyi People's Hospital, Dezhou, China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Linyi People's Hospital, Dezhou, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Jian
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Weiwen
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Qiyun
authors.initials: Q
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002299:Cardia / Q000473:pathology; D045744:Cell Line, Tumor; D008078:Cholesterol, LDL / Q000097:blood; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015994:Incidence; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D000071449:Proprotein Convertase 9 / Q000235:genetics*; D012189:Retrospective Studies; D012727:Sex Characteristics; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D008078:Cholesterol, LDL; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: LDL-C; NENs; PCSK9; epidemiology; miR-224