High expression of NEK2 promotes gastric cancer progression via activating AKT signaling

Wan, Hao; Xu, Lin; Zhang, Huangbin; Wu, Feixiang; Zeng, Weiqiang; Li, Taiyuan

doi:10.1007/s13105-020-00776-8

Cited by 15 publications

(9 citation statements)

References 36 publications

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“…10 Inactivating AKT by NEK2 silencing decreases aerobic glycolysis and promotes autophagic cell death, which eventually inhibits the growth of gastric cancer cell. 11 To our knowledge, this is the first study of the role of NEK2 in ccRCC. According to UALCAN database, NEK2 was highly expressed in ccRCC, which was confirmed at the protein level by IHC.…”

Section: Discussionmentioning

confidence: 85%

Overexpression of NEK2 is correlated with poor prognosis in human clear cell renal cell carcinoma

Wang

Huang

et al. 2021

Int J Immunopathol Pharmacol

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Objectives: Never in mitosis gene A-related kinase 2 (NEK2) has been implicated in tumorigenesis in various tissues, but its function in clear cell renal cell carcinoma (ccRCC) tumorigenesis is unclear. We evaluated the correlation between NEK2 expression and ccRCC. Methods: Immunohistochemistry analysis of NEK2 protein was done on high-density multi-organ Human Cancer tissue microarray derived from the patient samples from clear cell renal cell carcinoma. We used multiple clinical cohorts to analyze the NEK2 immunohistochemical staining expression across human cancers. The cancer genome atlas (TCGA) data analysis of NEK2 was done through UALCAN web servers. Association of NEK2 and Kaplan–Meier survival analysis was done on both of our clinical database and available TCGA datasets. Results: Using the UALCAN cancer transcriptional data analysis website, we found that NEK2 is overexpressed in ccRCC, and its expression was associated with overall survival. According to the analyses of our own clinical database and immunohistochemical staining, protein levels of NEK2 were elevated in renal carcinoma compared to adjacent normal tissues. Kaplan–Meier survival analysis of both UALCAN and our database showed that high expression of NEK2 was associated with a poor prognosis. Multivariate and univariate analyses showed that NEK2 expression was closely related to a poor prognosis. The findings suggest that NEK2 is associated with ccRCC. Conclusion: These studies show that NEK2 is over-expressed in clear cell renal cell carcinoma and plays an essential role in cancer cell survival, as such NEK2 could serve as a novel potential target for therapeutic intervention in ccRCC.

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Section: Discussionmentioning

confidence: 85%

Overexpression of NEK2 is correlated with poor prognosis in human clear cell renal cell carcinoma

Wang

Huang

et al. 2021

Int J Immunopathol Pharmacol

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“…Previous studies have identified abnormal levels of NEK2 proteins in a series of tumors, and NEK2 is involved in cell growth and apoptosis, enhances the ability of tumor invasion, and reduces the sensitivity of tumor cells to chemotherapeutic agents, thereby contributing to the tumorigenic capacity of malignant tumors [ 22 , 23 ]. Through the inactivation of the AKT pathway, NEK2 silencing hindered gastric cancer cell growth by inducing autophagic cell death and suppressing aerobic glycolysis [ 24 ]. In the study of NSCLC, NEK2 not only mediated tumor angiogenesis and M2 polarization of macrophages but also contributes to tumor cell proliferation and invasion, thus promoting the occurrence of nonsmall-cell lung cancer [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

NEK2 Serves as a Novel Biomarker and Enhances the Tumorigenicity of Clear-CellRenal-Cell Carcinoma by Activating WNT/β-Catenin Pathway

Zhou

Lai

Cheng

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Currently, cumulative evidence has shown that loss of NEK2 function suppresses tumor growth. However, complete studies on the regulatory role of NEK2 in clear-cellrenal-cell carcinoma (ccRCC) are rarely reported. Methods. The GEPIA database was used for information mining to analyze the gene expression differences between ccRCC tumor and normal tissues. At the same time, we analyzed the protein expression of NEK2 in clinical ccRCC samples and ccRCC cell lines. We detected the effect of NEK2 on the biological behavior of ccRCC at the cell level and further verified the biological effect of NEK2 on ccRCC cells in vivo by nude mouse tumorigenesis experiment. The expression of WNT/β-cateninpathway-related proteins and downstream proteins related to cell function were detected by Western blotting. Results. Using the GEPIA database, we observed that NEK2 expression level in ccRCC tissues was significantly higher than that in normal kidney tissues and was also related to tumor grade. The survival time of patients with ccRCC with high NEK2 expression was shorter than that of patients with low NEK2 expression. Compared with adjacent carcinoma and normal renal tubular epithelial cells, NEK2 levels were highly expressed in ccRCC tissues and ccRCC cell lines. NEK2 interference restrained ccRCC cell growth, migration, and invasion. NEK2 regulated the malignant behavior of ccRCC cells through the WNT/β-catenin pathway. Nude mouse tumorigenesis assay results showed that the transplanted tumors from NEK2 silenced mice grew more slowly and were smaller in size than those from control mice. Conclusions. NEK2 elevation may be associated with poor prognosis in ccRCC, and NEK2 enhances ccRCC cell proliferation, migration, and invasion ability by activating the WNT/β-catenin signaling pathway.

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“…Cbl-b regulates the levels of IFN-γ ( Li et al, 2019b ). IFN-γ is possibly involved in the pathogenesis of IBS-D after infection ( He et al, 2018 ); Nek2 is involved in the pathogenesis of IBS-D by activating the AKT pathway ( Wan et al, 2021 ) pathway ( Xia et al, 2021 ); Nde1 is involved in the pathogenesis of IBS-D by regulating the MAPK pathway ( Lanctot et al, 2013 ) ( Xia et al, 2021 ); Cep131 ( Wang et al, 2020 ), Tgfb2 ( Guo et al, 2016 ), Qsox1 ( Geng et al, 2020 ) mediate IBS-D pathogenesis through activation of PI3K/AKT pathway as well as other factors ( Guo et al, 2020b ). The above pathways as well as core genes are reflected in bioinformatic analysis to have an important relationship with the pathogenesis of IBS-D and are important components of the pathogenesis of IBS-D. At the same time, our qPCR experiment also verified that the expression of miR-6324 in the IBS-D model group decreased, which was the same as our previous high-throughput sequencing results.…”

Section: Discussionmentioning

confidence: 99%

Study on the pathogenesis of MiR-6324 regulating diarrheal irritable bowel syndrome and bioinformatics analysis

Jin

Zhou²,

Yang³

et al. 2023

Front. Pharmacol.

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Objective: To investigate the pathogenesis of IBS-D by bioinformatics analysis of the differential microRNAs in rat colon tissue and to analyze and predict the function of their target genes.Methods: Twenty male Wistar rats of SPF class were randomly divided into two groups, the model group was manipulated using the colorectal dilatation method + chronic restraint stress method to establish the IBS-D model; while the blank group stroked the perineum at the same frequency. Screening of differential miRNAs after High-throughput sequencing of rat colon tissue. GO and KEGG analysis of target genes using the DAVID website, further mapping using RStudio software; the STRING database and the Cytoscape software were used to obtain the protein interaction network (PPI) of the target genes as well as the core genes. Finally, qPCR was used to detect the expression of target genes in the colon tissue of two groups of rats.Results: After the screening, miR-6324 was obtained as the key of this study. The GO analysis of target genes of miR-6324 is mainly involved in protein phosphorylation, positive regulation of cell proliferation, and intracellular signal transduction; it affects a variety of cellular components such as cytoplasm, nucleus, and organelles on the intracellular surface; it is also involved in molecular functions such as protein binding, ATP binding, and DNA binding. KEGG analysis showed that the intersecting target genes were mainly enriched in cancer pathways, proteoglycans in cancer, neurotrophic signaling pathway, etc. The protein-protein interaction network screened out the core genes mainly Ube2k, Rnf41, Cblb, Nek2, Nde1, Cep131, Tgfb2, Qsox1, and Tmsb4x. The qPCR results showed that the expression of miR-6324 decreased in the model group, but the decrease was not significant.Conclusion: miR-6324 may be involved in the pathogenesis of IBS-D as a potential biological target and provide further ideas for research on the pathogenesis of the disease or treatment options.

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High expression of NEK2 promotes gastric cancer progression via activating AKT signaling

Cited by 15 publications

References 36 publications

Overexpression of NEK2 is correlated with poor prognosis in human clear cell renal cell carcinoma

Overexpression of NEK2 is correlated with poor prognosis in human clear cell renal cell carcinoma

NEK2 Serves as a Novel Biomarker and Enhances the Tumorigenicity of Clear-CellRenal-Cell Carcinoma by Activating WNT/β-Catenin Pathway

Study on the pathogenesis of MiR-6324 regulating diarrheal irritable bowel syndrome and bioinformatics analysis

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