Inhibition of Cyclin F Promotes Cellular Senescence through Cyclin-dependent Kinase 1-mediated Cell Cycle Regulation

作     者：Xun LI You-jian LI Meng-jie WANG Ke-peng OU Ya-qi CHEN Xun LI;You-jian LI;Meng-jie WANG;Ke-peng OU;Ya-qi CHEN

作者机构：GI Cancer Research InstituteTongji HospitalHuazhong University of Science and TechnologyWuhan430030China College of PharmacyNational&Local Joint Engineering Research Center of Targeted and Innovative TherapeuticsChongqing Key Laboratory of Kinase Modulators as Innovative MedicineChongqing University of Arts and SciencesChongqing402160China Department of Obstetrics and GynecologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China College of Pharmaceutical Sciences and Chinese MedicineSouthwest UniversityChongqing400715China 

出 版 物：《Current Medical Science》 (当代医学科学（英文）)

年 卷 期：2023年第43卷第2期

页      面：246-254页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.81874148 and No.82203142). 

主　　题：cyclin F kidney renal clear cell carcinoma clinical outcome cyclin-dependent kinase 1 senescence 

摘      要：Objective Kidney renal clear cell carcinoma(KIRC)is a common renal malignancy that has a poor prognosis.As a member of the F box family,cyclin F(CCNF)plays an important regulatory role in normal tissues and tumors.However,the underlying mechanism by which CCNF promotes KIRC proliferation still remains unclear.Methods Bioinformatics methods were used to analyze The Cancer Genome Atlas(TCGA)database to obtain gene expression and clinical prognosis data.The CCK8 assay,EdU assay,and xenograft assay were used to detect cell proliferation.The cell senescence and potential mechanism were assessed by SA-β-gal staining,Western blotting,as well as ELISA.Results Our data showed that CCNF was highly expressed in KIRC patients.Meanwhile,downregulation of CCNF inhibited cell proliferation in vivo and in vitro.Further studies showed that the reduction of CCNF promoted cell senescence by decreasing cyclin-dependent kinase 1(CDK1),increasing the proinflammatory factors interleukin(IL)-6 and IL-8,and then enhancing the expression of p21 and p53.Conclusion We propose that the high expression of CCNF in KIRC may play a key role in tumorigenesis by regulating cell senescence.Therefore,CCNF shows promise as a new biomarker to predict the clinical prognosis of KIRC patients and as an effective therapeutic target.