Research Papers:

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

Jian’an Bai, He Na, Xiumei Hua, Yaling Wei, Tian Ye, Yiqiang Zhang, Guo Jian, Weiwen Zeng, Lijun Yan and Qiyun Tang _

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Oncotarget. 2017; 8:6929-6939. https://doi.org/10.18632/oncotarget.14322

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Jian’an Bai1, He Na2, Xiumei Hua2, Yaling Wei2, Tian Ye1, Yiqiang Zhang3, Guo Jian4, Weiwen Zeng2, Lijun Yan2, Qiyun Tang2

1Department of Gastroenterology, Sir Run Run Hospital Affiliated with Nanjing Medical University, Nanjing, China

2Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Department of Radiology, Linyi People's Hospital, Dezhou, China

4Department of Orthopaedics, Linyi People’s Hospital, Dezhou, China

Correspondence to:

Qiyun Tang, email: [email protected]

Keywords: NENs, epidemiology, LDL-C, PCSK9, miR-224

Received: February 29, 2016     Accepted: December 16, 2016     Published: December 28, 2016


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).

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