任换平
细胞衰老调控:环蛋白F在肾癌治疗中的新视角
2024-7-9 12:14
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Inhibition of Cyclin F Promotes Cellular Senescence through Cyclin-dependent Kinase 1-mediated Cell Cycle Regulation

作者:Xun Li, You-jian Li, Meng-jie Wang, Ke-peng Ou & Ya-qi Chen

编辑荐读

本文揭示了环蛋白F(CCNF)在肾透明细胞癌(KIRC)中的重要作用,以及其通过CDK1-p53/p21信号通路调控细胞衰老的机制,研究团队来自华中科技大学同济医学院附属同济医院。这项研究不仅为我们理解KIRC的分子机制提供了新的视角,更为开发新的诊断标志物和治疗策略提供了科学依据。相信这篇论文将激发更多关于KIRC的研究和讨论,为战胜这一疾病提供新的思考和方法。

研究亮点:

创新性:首次揭示了CCNF在KIRC中的高表达与肿瘤增殖之间的直接联系。

机制阐释: 深入分析了CCNF通过调控CDK1-p53/p21信号通路影响细胞衰老的分子机制。

临床应用:提供了KIRC潜在的生物标志物和治疗靶点,具有重要的临床转化潜力。

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

/Abstract

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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.

ResultsOur 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.ConclusionWe 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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