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

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Abstract

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.

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Correspondence to Ya-qi Chen.

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Conflict of Interest Statement

The authors declare that they have no conflicts of interest regarding the publication of this paper.

This study was supported by the National Natural Science Foundation of China (No. 81874148 and No. 82203142).

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Li, X., Li, Yj., Wang, Mj. et al. Inhibition of Cyclin F Promotes Cellular Senescence through Cyclin-dependent Kinase 1-mediated Cell Cycle Regulation. CURR MED SCI 43, 246–254 (2023). https://doi.org/10.1007/s11596-022-2692-3

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  • DOI: https://doi.org/10.1007/s11596-022-2692-3

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