Cancer Management and Research (Dec 2020)
NUCKS1 Promotes Proliferation, Invasion and Migration of Non-Small Cell Lung Cancer by Upregulating CDK1 Expression
Abstract
Shufen Zhao,1 Baiyao Wang,2 Yanning Ma,3 Junjie Kuang,1 Jiyun Liang,3 Yawei Yuan1,2 1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province 510515, People’s Republic of China; 2Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou City, Guangdong Province 510095, People’s Republic of China; 3Shunde Hospital, Southern Medical University, Foshan City, Guangdong Province 528308, People’s Republic of ChinaCorrespondence: Yawei YuanNanfang Hospital, Southern Medical University, 1838 Guangzhou Dadao North, Guangzhou City, Guangdong Province 510515, People’s Republic of ChinaEmail [email protected]: 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 overexpression promoted proliferation, invasion and migration of both A549 and NCI-H460 cells while NUCKS1 knockdown displayed the opposite effects. Moreover, the results of the xenograft 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 proliferation, invasion and migration.Conclusion: Taken together, these findings demonstrated that NUCKS1 promotes proliferation, invasion and migration of NSCLC by upregulating CDK1, providing a novel putative target for the clinical treatment of NSCLC.Keywords: non-small cell lung cancer, NUCKS1, proliferation, migration, CDK1
