NIMA related kinase 2 promotes gastric cancer cell proliferationviaERK/MAPK signaling

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.

RETRACTED: Exosome-Derived miR-486-5p Regulates Cell Cycle, Proliferation and Metastasis in Lung Adenocarcinoma via Targeting NEK2

“…NEK2 has been reported to function as an oncogene in diverse cancers, and it exhibits an intimate correlation with the drug resistance of tumors. In hepatocellular carcinoma (HCC), for example, NEK2 activates the transcription of downstream target genes through stabilizing β-catenin and promoting its translocation to the nucleus, consequently enhancing the sorafenib resistance in HCC cells (Deng et al, 2019). reported that NEK2 potentiated the malignant proliferation of gastric cancer cells via the ERK/MAPK axis.…”

RPL17 Promotes Colorectal Cancer Proliferation and Stemness through ERK and NEK2/β-catenin Signaling Pathways

“…Consistent with our observation, it was previously demonstrated that NEK2 silencing decreases proliferation and induces apoptosis in CRC cells 18 and that NEK2 regulates Wnt/β-catenin signaling pathway which plays a pivotal role in exerting cancer stemness 14 , 19 . It was also found that ERK is functionally associated with NEK2 expression and knockdown of NEK2 inhibits ERK phosphorylation in gastric cancer cells 20 . Western blotting validated that silencing of RPL17 expression reduces the levels of NEK2/β-catenin and the activity of ERK in both HCT116 and HT29 cells (Fig.…”

“…These data indicate that although RPL17 is involved in protein synthesis, it does not affect entire cellular protein biosynthesis, it is rather gene-specific and protein-specific. Of all the genes that were dysregulated by RPL17 knockdown, oncogenic NEK2, which is known to regulate ERK phosphorylation for cell survival 20 , was down-regulated in network 2 of the IPA (Fig. 7 C).…”

High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms

“…However, data from other cancers indicate that NEK2 and PIM1 kinases possess oncogenic potential and that they interact with diverse downstream signaling pathways. In vitro studies have shown that NEK2 promotes cell proliferation by AKT and Wnt activation in NSCLC [ 45 ] and hepatocellular carcinoma [ 46 ] and via ERK/MAPK (extracellular signal-regulated kinase/mitogen-activated protein kinase) signaling in gastric cancer [ 47 ]. Moreover, NEK2 deregulation was found to act as drivers of tumorigenesis in breast cancer by induction of centrosome amplification [ 16 ].…”