Published online Jun 21, 2019. doi: 10.3748/wjg.v25.i23.2898
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
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.
To determine the role of the up-regulation of NEK2 in GC.
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.
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.
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.
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.