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Inhibition of cyclin f Promotes Cellular Senescence through cyclin-dependent Kinase 1-mediated Cell Cycle Regulation

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Current Medical Science 2023年第2期43卷 246-254页

作者： Xun LI You-jian LI Meng-jie WANG Ke-peng OU Ya-qi CHEN GI Cancer Research Institute Tongji HospitalHuazhong University of Science and TechnologyWuhan430030China College of Pharmacy National&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 Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China College of Pharmaceutical Sciences and Chinese Medicine Southwest UniversityChongqing400715China

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.

关键词： cyclin f kidney renal clear cell carcinoma clinical outcome cyclin-dependent kinase 1 senescence

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