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

Li, Xun; Li, You-Jian; Wang, Meng-Jie; Ou, Kepeng; Chen, Yaqi

doi:10.1007/s11596-022-2692-3

Cited by 3 publications

(3 citation statements)

References 22 publications

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“…CDK1 is also affected by the proportion of FOXM1 and KIF20A overexpression 54 , which further highlights their decisive roles in the cell division and mitosis. In fact, our functional analyses are consistent with recent in silico and in vitro studies of Li et al, who showed that CCNF might promote ccRCC proliferation by inhibiting cell senescence through the CDK1-P53 signaling pathway 33 . Taken together, it appears that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation, thus targeting the cyclin F offers a potential novel strategy to target the ccRCC cells efficiently.…”

Section: Discussionsupporting

confidence: 91%

Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma

Kwiatkowski,

Krajewski,

Durślewicz

et al. 2024

Sci Rep

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Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC.

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Section: Discussionsupporting

confidence: 91%

Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma

Kwiatkowski,

Krajewski,

Durślewicz

et al. 2024

Sci Rep

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show abstract

“…Our in vitro experimental results provided evidence to support that aberrant CDK1 upregulation inhibited cellular senescence and promoted cell proliferation. This finding is well consistent with CDK1 anti‐senescence role in other cancer contexts including gastrointestinal stromal tumor and renal clear cell carcinoma 40,47 . These abovementioned findings suggest these SRGs identified here might have oncogenic or tumor‐suppressive roles underlying OSCC progression by modulating cell senescence, which deserve further experimental explorations.…”

Section: Discussionsupporting

confidence: 89%

“…This finding is well consistent with CDK1 anti-senescence role in other cancer contexts including gastrointestinal stromal tumor and renal clear cell carcinoma. 40,47 These abovementioned findings suggest these SRGs identified here might have oncogenic or tumorsuppressive roles underlying OSCC progression by Accumulating evidence has demonstrated a superior prognostic value of optimized combination of SRGsderived signature in multiple cancers. 14,48 We have effectively developed and verified a 7-SRGs OSCC-specific prognostic signature with favorable prognostic powers in multiple independent patient cohorts as supported by ROC and C-index analyses.…”

Section: Discussionmentioning

confidence: 58%

Development of a novel senescence‐related gene signature to predict clinical outcomes, immune landscape, and chemotherapeutic sensitivity in oral squamous cell carcinoma

Wang,

Xiao,

Wang

et al. 2024

Head & Neck

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BackgroundCellular senescence significantly associates with tumor initiation, progression, and therapeutic response across multiple cancers. Here, we sought to develop a novel senescence‐related genes (SRGs)‐derived signature for oral squamous cell carcinoma (OSCC) prognostication and therapeutic response prediction.MethodsOSCC‐specific SRG prognostic signature was established with univariate Cox regression, Kaplan–Meier survival, and LASSO‐penalized multivariate Cox regression analyses. A SRG nomogram integrating this signature and selected clinicopathological parameters were constructed by multivariate Cox regression. SiRNA‐mediated gene knockdown was exploited to validate its function in vitro. The utilities of SRG signature in predicting immune status and chemotherapeutic sensitivities were analyzed.ResultsThe prognostic performance of SRG signature/nomogram was satisfactory in multiple independent cohorts. CDK1 knockdown induced senescence phenotype in vitro. Moreover, SRG signature scores negatively correlated with tumor‐infiltrating immune cells and associated with multiple chemotherapeutic drug sensitivities.ConclusionsOur results established SRG‐derived signature/nomogram as powerful predictors for prognosis and chemotherapeutic response for OSCC.

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A Predictive Model Based on the FBXO Family Reveals the Significance of Cyclin F in Hepatocellular Carcinoma

Gao,

Li,

Guo

et al. 2024

Front. Biosci. (Landmark Ed)

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Objective: The F-box protein (FBXO) family plays a key role in the malignant progression of tumors. However, the biological functions and clinical value of the FBXO family in liver cancer remain unclear. Our study comprehensively assessed the clinical value of the FBXO family in hepatocellular carcinoma (HCC) and constructed a novel signature based on the FBXO family to predict prognosis and guide precision immunotherapy. Methods: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the expression characteristics and prognostic value of the FBXO family in HCC. A predictive model based on the FBXO family using TCGA database; and its predictive ability was validated using the ICGC database. Further analyses revealed that this predictive model can independently predict the overall survival (OS) rate of patients with HCC. We further analyzed the association of this predictive model with signaling pathways, clinical pathological features, somatic mutations, and immune therapy responses. Finally, we validated the biological functions of cyclin F (CCNF) through in vitro experiments. Results: A predictive model involving three genes (CCNF, FBXO43, and FBXO45) was constructed, effectively identifying high and low-risk patients with differences in OS, clinicopathological characteristics, somatic mutations, and immune cell infiltration status. Additionally, knock-down of CCNF in HCC cell lines reduced cell proliferation in vitro, suggesting that CCNF may be a potential therapeutic target for HCC. Conclusions: The predictive model based on the FBXO family can effectively predict OS and the immune therapy response in HCC. Additionally, CCNF is a potential therapeutic target for HCC.

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

Cited by 3 publications

References 22 publications

Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma

Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma

Development of a novel senescence‐related gene signature to predict clinical outcomes, immune landscape, and chemotherapeutic sensitivity in oral squamous cell carcinoma

A Predictive Model Based on the FBXO Family Reveals the Significance of Cyclin F in Hepatocellular Carcinoma

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