Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2019; 25(23): 2898-2910
Published online Jun 21, 2019. doi: 10.3748/wjg.v25.i23.2898
NIMA related kinase 2 promotes gastric cancer cell proliferation via ERK/MAPK signaling
Wei-Dong Fan, Tao Chen, Peng-Jun Liu
Wei-Dong Fan, Department of Gastroenterology, the Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, Jiangsu Province, China
Tao Chen, Peng-Jun Liu, Department of Gastroenterology, the Wujin Hospital Affiliated to Jiangsu University, Changzhou 213002, Jiangsu Province, China
Author contributions: Fan WD and Liu PJ designed the research; Fan WD and Chen T performed the research; Fan WD and Chen T analyzed the data; Liu PJ wrote the paper.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of the Wujin Hospital Affiliated to Jiangsu University.
Conflict-of-interest statement: The authors declare no financial and personal relationships with other people or organizations.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Peng-Jun Liu, MD, Attending Doctor, Chief Doctor, Department of Gastroenterology, the Wujin Hospital Affiliated to Jiangsu University, No. 2, Yongning North Road, Changzhou 213002, Jiangsu Province, China. lpjlx2008@126.com
Telephone: +86-519-5336190 Fax: +86-519-5336190
Received: April 4, 2019
Peer-review started: April 4, 2019
First decision: April 11, 2019
Revised: April 27, 2019
Accepted: May 18, 2019
Article in press: May 18, 2019
Published online: June 21, 2019
Processing time: 78 Days and 11.4 Hours
Abstract
BACKGROUND

NIMA related kinase 2 (NEK2) is closely related to mitosis, and it is currently considered to be over-expressed frequently in many poorly prognostic cancers. However, the effect of the up-regulated NEK2 on cellular signaling in tumors, such as gastric cancer (GC), is con-fusing.

AIM

To determine the role of the up-regulation of NEK2 in GC.

METHODS

To investigate the pathological significance of NEK2 in GC, the expression pattern of NEK2 in GC was investigated based on the “Oncomain” database and compared between 30 pairs of cancer samples and adjacent tissues. The co-expression of NEK2 and ERK in GC was analyzed using The Cancer Genome Atlas (TCGA) database and confirmed in clinical samples by quantitative real-time PCR (qRT-PCR), and the survival curve was also plotted. Western blot or qRT-PCR was used to analyze the effect of NEK2 on the phosphorylation levels of ERK and c-JUN in two GC cell lines (BGC823 and SGC7901) with NEK2 overexpression, and the expression of the downstream effector cyclin D1. Furthermore, CCK8, EdU incorporation assay, and flow cytometry were used to detect the proliferative ability of BGC823 and SGC7901 cells with stably silenced ERK.

RESULTS

NEK2 was significantly up-regulated in human GC tissues. ERK was significantly associated with NEK2 expression in human clinical specimens, and combined overexpression of NEK2 and ERK potentially forecasted a poor prognosis and survival in GC patients. NEK2 knockdown in GC cells inhibited ERK and c-JUN phosphory-lation and reduced the transcription of cyclin D1. More interestingly, NEK2 can rescue the inhibition of cellular viability, proliferation, and cell cycle progression due to ERK knockdown.

CONCLUSION

Our results indicate that NEK2 plays a carcinogenic role in the malignant proliferation of GC cells via the ERK/MAPK signaling, which may be important for treatment and improving patient survival.

Keywords: NIMA related kinase 2; ERK/MAPK signaling; Cyclin D1; Cell proliferation; Gastric cancer

Core tip: Expression of NIMA related kinase 2 (NEK2) is significantly up-regulated in human gastric cancer (GC) tissues and cells. Combined NEK2 and ERK expression may predict overall survival in patients with GC. NEK2 regulates the expression of cyclin D1 by affecting the phosphorylation of ERK and c-JUN in GC and mediates cell proliferation via the ERK/c-JUN/cyclin D1 axis.