4.6 Article

NEK2 is associated with poor prognosis of clear cell renal cell carcinoma and promotes tumor cell growth and metastasis

Journal

GENE
Volume 851, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.gene.2022.147040

Keywords

Never in Mitosis gene-A (NIMA)-related Kinase; 2 (NEK2); Clear cell renal cell carcinoma (ccRCC); Proliferation; Migration; Invasion

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NEK2 is highly expressed in clear cell renal cell carcinoma (ccRCC), and its expression is associated with clinical outcomes. NEK2 plays an important role in regulating cell proliferation and metastasis in ccRCC.
Background: Never in Mitosis gene-A (NIMA)-related Kinase 2 (NEK2) is a critical player in the mitotic processes. NEK2 is highly expressed in many kinds of human cancers and has been shown to participate in drug resistance, tumorigenesis, and tumor progression. However, the expression or function of NEK2 in clear cell renal cell carcinoma (ccRCC) has not yet been investigated.Methods: We used TCGA database to study the NEK2 expression in ccRCC. The expression of NEK2 in tumor tissues and adjacent tissues was examined by immunohistochemistry. We also analysed the correlation between NEK2 expression and clinical parameters of ccRCC. The mRNA and protein level of NEK2 expression were semi -quantified by qRT-PCR and western blotting analysis. Following NEK2 knockdown by RNA interference in Caki-1 cells, while NEK2 overexpression in A489 cells, CCK8 and transwell assay was used to confirm the prolifera-tion, migration and invasion, respectively. Finally, our in vivo study were carried out using nude mice to establish mouse model for kidney cancer.Results: We observed elevated expression of NEK2 both in ccRCC tumor tissues and cell lines. Together with clinical and pathological features, our analysis indicated a clear association of clinical outcomes between ccRCC patients with high and low NEK2 expression. Our in vitro studies demonstrated that NEK2 knockdown inhibits the proliferation, migration and invasion of Caki-1 cells, oppositely, overexpression of NEK2 promotes the pro-liferation, migration and invasion of A489 cells. In the end, our animal study demonstrated that deletion of NEK2 expression could impair tumor growth.Conclusion: Our data suggested that NEK2 was important in regulating ccRCC cell proliferation and metastasis, and indicated NEK2 as a potentially important target for the treatment of ccRCC.

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