Cyclin F Downregulation Affects Epithelial-Mesenchymal Transition Increasing Proliferation and Migration of the A-375 Melanoma Cell Line

Krajewski, Adrian; Gagat, Maciej; Mikołajczyk, Klaudia; Izdebska, Magdalena; Żuryń, Agnieszka; Grzanka, Alina

doi:10.2147/cmar.s279169

Cited by 7 publications

(4 citation statements)

References 46 publications

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“…Cyclin F CDK, reduced by eugenol, is know to be capable of initiating checkpoint response in G2 65 and to ensure mitosis fidelity through control of centrosome duplication 66 . Dual roles have been described for cyclin F 67 , 68 , and our results follow the example of the ovarian cancer where cyclin F enhanced proliferation and invasion of cancer cells and was linked with a poor prognosis in patients 68 . Another extensively described checkpoint process downregulated by eugenol involves the APC2 (also known as ANAPC2) catalytic subunit of the anaphase promoting complex (APC/C).…”

Section: Discussionsupporting

confidence: 87%

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

Issa,

Loubaki,

Al Amri

et al. 2024

Sci Rep

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Adoption of plant-derived compounds for the management of oral cancer is encouraged by the scientific community due to emerging chemoresistance and conventional treatments adverse effects. Considering that very few studies investigated eugenol clinical relevance for gingival carcinoma, we ought to explore its selectivity and performance according to aggressiveness level. For this purpose, non-oncogenic human oral epithelial cells (GMSM-K) were used together with the Tongue (SCC-9) and Gingival (Ca9-22) squamous cell carcinoma lines to assess key tumorigenesis processes. Overall, eugenol inhibited cell proliferation and colony formation while inducing cytotoxicity in cancer cells as compared to normal counterparts. The recorded effect was greater in gingival carcinoma and appears to be mediated through apoptosis induction and promotion of p21/p27/cyclin D1 modulation and subsequent Ca9-22 cell cycle arrest at the G0/G1 phase, in a p53-independent manner. At these levels, distinct genetic profiles were uncovered for both cell lines by QPCR array. Moreover, it seems that our active component limited Ca9-22 and SCC-9 cell migration respectively through MMP1/3 downregulation and stimulation of inactive MMPs complex formation. Finally, Ca9-22 behaviour appears to be mainly modulated by the P38/STAT5/NFkB pathways. In summary, we can disclose that eugenol is cancer selective and that its mediated anti-cancer mechanisms vary according to the cell line with gingival squamous cell carcinoma being more sensitive to this phytotherapy agent.

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Section: Discussionsupporting

confidence: 87%

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

Issa,

Loubaki,

Al Amri

et al. 2024

Sci Rep

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“…CCNF is an important factor involved in regulating apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT). Increasing evidence suggests that its dysregulation can contribute to the evasion of apoptosis, promotion of angiogenesis, and acquisition of invasiveness by cancer cells 20 , 21 . In this study, we conducted a comprehensive multi-omics analysis to investigate the intricate association between CCNF and pan-cancer.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Analysis of the Prognostic, Immunological and Diagnostic Role of CCNF in Pan-cancer

Gao¹,

Bu²,

Ge³

et al. 2023

J. Cancer

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Background: Cyclin F (CCNF) represents a pivotal constituent within the family of cell cycle proteins, which also belongs to the F-box protein family and acts as a critical regulatory factor in cell cycle transition. Its heightened expression has been consistently identified across various cancer types, including breast, pancreatic, and colorectal cancer. Nonetheless, a comprehensive exploration of CCNF's involvement in pan-cancer remains lacking. Methods: This study collected transcriptomic data and clinical information from several databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and BioGPS detabase. Employing bioinformatics methods, we investigated the potential oncogenic role of CCNF, utilizing various databases such as cBioPortal, Human Protein Atlas (HPA), TIMER2, UALCAN, GEPIA, GSCALite, and CTD detabase. These analyses focused on exploring CCNF expression, prognosis, gene mutations, immune cell infiltration, DNA methylation levels, and targeted chemical drugs across different tumor types. Additionally, we obtained CCNF-related genes from GeneMANIA and GEPIA databases and conducted GO and KEGG enrichment analyses to gain deeper insights into the biological processes associated with CCNF. Furthermore, we validated the differential expression of CCNF in normal human breast cancer and breast cancer cell lines using experimental verification. Results: CCNF exhibited upregulation in the majority of cancer types, demonstrating early diagnostic potential in 15 cancers and prognostic implications for adverse outcomes across numerous malignancies. Furthermore, CCNF was found to be linked with markers of the tumor immune microenvironment in various cancers. Additionally, CCNF expression influenced genetic alterations in pan-cancer. Enrichment analysis revealed that CCNF primarily participates in crucial biological pathways such as the cell cycle, p53 signaling pathway, and cellular senescence pathways. RT-qpcr and WB assays further confirmed that CCNF expression was higher in human cancer cell lines than in normal cell lines. Conclusion: The underlying role and mechanism of CCNF in pan-cancer were elucidated through comprehensive bioinformatics analysis and experimental validation. CCNF holds promise as an invaluable early detection indicator and tumor biomarker, offering potential targets for tumor treatment and prevention.

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“…After cyclin F silencing, we observed an increased proliferation rate and elevated capabilities for migration and invasion. Additionally, the morphological and molecular alterations suggested the induction of the process similar to epithelial-to-mesenchymal transition in the A375 melanoma cell line 12 , 39 . In pancreatic adenocarcinoma, high CCNF mRNA was associated with poor prognosis, whereas the univariable Cox proportional hazards model pointed to cyclin F protein as a favorable prognostic marker; however, the last observation was not statistically significant 37 .…”

Section: Discussionmentioning

confidence: 94%

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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Cyclin F Downregulation Affects Epithelial-Mesenchymal Transition Increasing Proliferation and Migration of the A-375 Melanoma Cell Line

Cited by 7 publications

References 46 publications

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

A Comprehensive Analysis of the Prognostic, Immunological and Diagnostic Role of CCNF in Pan-cancer

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

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