RFC4通过调控DNA损伤反应赋予食管鳞状细胞癌放射抗性

IF 5 2区 生物学 Q2 CELL BIOLOGY
Tao Yang, Yue Fan, Guang Bai, Yinpeng Huang
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引用次数: 0

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RFC4 confers radioresistance of esophagus squamous cell carcinoma through regulating DNA damage response.

Radioresistance in esophageal squamous cell carcinoma (ESCC) is a critical factor leading to treatment failure and recurrence, yet its underlying molecular mechanisms remain unclear. This study aimed to investigate the role of Replication Factor C4 (RFC4) in ESCC radioresistance and to explore the underlying mechanisms. We utilized online bioinformatics tools to analyze the properties, functions, and prognostic significance of RFC4 in ESCC. We established cell lines with varying RFC4 expression levels and subjected them to radiation exposure. RFC4 expression was assessed using quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunoblotting. Cell proliferation was evaluated with MTT, EdU, and colony formation assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting and immunofluorescence were used to study the impact of RFC4 on the DNA damage response in ESCC cells. A xenograft mouse model was employed to assess tumor growth in vivo. RFC4 expression was significantly upregulated in ESCC tissues and cells, particularly in radioresistant cases. Functional experiments revealed that RFC4 promotes cell proliferation, inhibits apoptosis, induces cell cycle arrest, and mitigates radiation-induced DNA damage responses. Mechanistically, RFC4-mediated radioresistance in ESCC may involve the inactivation of the p53 signaling pathway. In animal studies, RFC4 knockdown, either alone or in combination with radiation therapy, effectively suppressed the growth of xenograft tumors. These findings highlight the potential of targeting RFC4 to overcome radioresistance by modulating the DNA damage response in ESCC, offering promising therapeutic avenues for ESCC patients.

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来源期刊
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
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