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

Abstract

BackgroundNever in Mitosis gene-A(NIMA)-related Kinase 2 (NEK2) is a critical player in themitotic processes. NEK2 is highly expressed in many kindsof human cancers and has been shown toparticipatein drug resistance, tumorigenesis, and tumor progression. However, the expression or function of NEK2 in clear cell renal cell carcinoma (ccRCC)hasnot yet been investigated. MethodsWeused TCGA databaseto study the NEK2 expression in ccRCC. The expression of NEK2 in tumor tissuesand adjacent tissueswas examined by immunohistochemistry. We also analysed the correlation between NEK2 expression and clinical parametersofccRCC. The mRNA and protein level of NEK2 expression were semi-quantifiedby qRT-PCR and western blotting analysis. Following NEK2 knockdown by RNA interference in Caki-1cells, whileNEK2 overexpression in A489 cells, CCK8and transwell assay was used to confirmtheproliferation, migration and invasion, respectively.Finally, our in vivo study were carried out using nudemice to establish mouse model for kidney cancer. ResultsWe observed elevated expression of NEK2 both in ccRCCtumor 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 lowNEK2expression. Our in vitro studies demonstratedthat NEK2 knockdowninhibits the proliferation,migrationand invasion of Caki-1cells, oppositely, overexpressionof NEK2 promotes the proliferation, migrationand invasion of A489cells.In the end, our animal study demonstrated that deletion of NEK2 expression could impair tumor growth. ConclusionOur data suggestedthat NEK2wasimportant inregulating ccRCC cell proliferation and metastasis, and indicated NEK2as a potentially important target for the treatment ofccRCC.