Gao Xiaofeng, Bu Huitong, Ge Juanjuan, Gao Xuzheng, Wang Ying, Zhang Zhenwang, Wang Long
School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Hubei University of Science and Technology, Xianning 437000, Hubei, PR China.
Medicine Research Institute /Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437000, Hubei, PR China.
J Cancer. 2023 Jul 31;14(13):2431-2442. doi: 10.7150/jca.86597. eCollection 2023.
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. 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. 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. 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.
细胞周期蛋白F（CCNF）是细胞周期蛋白家族中的关键组成部分，它也属于F-box蛋白家族，是细胞周期转换中的关键调节因子。在包括乳腺癌、胰腺癌和结直肠癌在内的多种癌症类型中，均持续发现其表达升高。然而，目前仍缺乏对CCNF在泛癌中作用的全面研究。本研究从多个数据库收集了转录组数据和临床信息，包括癌症基因组图谱（TCGA）、基因型-组织表达（GTEx）和BioGPS数据库。我们运用生物信息学方法，利用诸如cBioPortal、人类蛋白质图谱（HPA）、TIMER2、UALCAN、GEPIA、GSCALite和CTD数据库等各种数据库，研究了CCNF的潜在致癌作用。这些分析聚焦于探究不同肿瘤类型中CCNF的表达、预后、基因突变、免疫细胞浸润、DNA甲基化水平以及靶向化学药物。此外，我们从GeneMANIA和GEPIA数据库中获取了与CCNF相关的基因，并进行了基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，以更深入地了解与CCNF相关的生物学过程。此外，我们通过实验验证，证实了CCNF在正常人类乳腺癌和乳腺癌细胞系中的差异表达。CCNF在大多数癌症类型中均表现出上调，在15种癌症中显示出早期诊断潜力，并对多种恶性肿瘤的不良预后具有预后意义。此外，在各种癌症中发现CCNF与肿瘤免疫微环境的标志物有关。此外，CCNF表达影响泛癌中的基因改变。富集分析表明，CCNF主要参与细胞周期、p53信号通路和细胞衰老通路等关键生物学途径。实时定量聚合酶链反应（RT-qpcr）和蛋白质免疫印迹（WB）检测进一步证实，CCNF在人类癌细胞系中的表达高于正常细胞系。通过全面的生物信息学分析和实验验证，阐明了CCNF在泛癌中的潜在作用和机制。CCNF有望成为一种宝贵的早期检测指标和肿瘤生物标志物，为肿瘤治疗和预防提供潜在靶点。
