Nucks1 promotes proliferation, invasion and migration of non-small cell lung cancer by upregulating cdk1 expression

Abstract

Background: Non-small cell lung cancer (NSCLC) is a predominant type of lung cancer with a high mortality rate. Objective: The aim of this study is to investigate the roles of nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) in NSCLC and to identify the potential mechanisms. Materials and Methods: The expression of NUCKS1 in several NSCLC cells was detected firstly. Then, NUCKS1 was overexpressed or silenced in both A549 and NCI-H460 cells, where cell proliferation, invasion and migration were, respectively, determined, using CCK-8, colony formation assay, transwell and wound healing assays. Cell cycle analysis was performed, and the expression-associated proteins were detected by Western blotting. Subsequently, NCI-H460 cells with NUCKS1 overexpression for the subsequent tumor-bearing experiment. And the NUCKS1 expression in tumor tissues was measured by means of immunohistochemistry and Western blotting. Additionally, the STRING database predicted that Cyclin-Dependent Kinase 1 (CDK1) would bind to NUSK1, which was verified by the co-immunoprecipitation assay. Then, CDK1 was silenced by transfection with short hairpin RNA (shRNA)-CDK-1 or by exposure to CDK1 inhibitor p2767-00. And the biological characteristics of proliferation, invasion and migration were examined. Results: Results indicated that NUCKS1 was overly expressed in NSCLC cells, and its over-expression promoted proliferation, invasion and migration of both A549 and NCI-H460 cells while NUCKS1 knockdown displayed the opposite effects. Moreover, the results of the xeno-graft experiments revealed that NUCKS1-upregulation promoted the tumor growth. Furthermore, the immunoprecipitation assay verified CDK1’s interaction with NUCKS1, and CDK1 knockdown alleviates the impact of NUCKS1 overexpression on NSCLC cell prolifera-tion, invasion and migration. Conclusion: Taken together, these findings demonstrated that NUCKS1 promotes prolifera-tion, invasion and migration of NSCLC by upregulating CDK1, providing a novel putative target for the clinical treatment of NSCLC.