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 overexpressed frequently in many poorly prognostic cancers. However, the effect of up-regulated NEK2 expression on cellular signaling in tumors, such as gastric cancer (GC), is confusing.
To explore the treatment of GC and improve patient survival.
To determine the role of the up-regulation of NEK2 in GC.
To investigate the pathological significance of NEK2 in GC, the expression of NEK2 in GC was investigated based on the “Oncomain” database and compared between 30 pairs of cancer and adjacent tissues. The co-expression of NEK2 and ERK in GC was analyzed based on the 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 BGC823 and SGC7901 cells, and the expression of the downstream effector cyclin D1. Furthermore, CCK8, EdU incorporation assay, and flow cytometry were used to detect the proliferative of BGC823 and SGC7901 cell lines with stable silencing of ERK.
In this study, we found that NEK2 was significantly up-regulated in human GC tissues. In addition, 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 pho-sphorylation and reduced transcription of cyclin D1. More interestingly, NEK2 can rescue the inhibition of cellular viability, proliferation, and cell cycle progression due to ERK knockdown.
NEK2 plays a carcinogenic role in the malignant proliferation of GC cells via the ERK/MAPK signaling, which is important for treating GC and improving patient survival.
Future research may further reveal the mechanism of action of NEK2 to enhance the sensitivity of cancer cells and promote its application in anti-cancer treatments. And the identification of the molecular pathway related to ERK/MAPK signaling may further elucidate the underlying mechanism.