NUCKS1 Promotes Proliferation,Invasion And Migration Of Non-small Cell Lung Cancer By Upregulating CDK1 Expression

Non-small cell lung cancer(NSCLC)is a common malignant tumor,which has the characteristics of easy metastasis and recurrence and high malignancy.According to the latest global cancer statistics 2020,there are 2.2 million new cases of lung cancer worldwide and 1.8 million deaths,ranking second in the incidence of malignant tumors(11.4%)and mortality(18.0%).As my country’s industrialization is accelerating,environmental pollution is becoming more serious,and the problem of population aging is intensifying,the incidence and mortality of lung cancer are increasing.According to statistics,the incidence and death of lung cancer in China accounted for 37.0%and 39.8%of the global total,and the 5-year survival rate was only 15%to 20%,which brought a serious burden to society and families.Therefore,the prevention and treatment of NSCLC is a major challenge that how to prevent and control of the occurrence and death of tumors in my country.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,colonyization formation assay,transwell and wound healing assays.Cell cycle analysis was performed to detect expression related proteins 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 Kinase1(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 overexpressed in NSCLC cells,and its overexpression promoted proliferation,invasion and migration of A549 and NCI-H460 cells,whereas NUCKS1 knockdown displayed the opposite effects.Moreover,results of the xenograft experiments revealed that NUCKS1-upregulation promotedthe 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:These findings demonstrated that NUCKS1 promotes NSCLC’sproliferation,invasion and migration by upregulating CDK1,that providing a novel putative target for the clinical treatment of NSCLC.