MDMX enhances radiosensitivity in lung adenocarcinoma and squamous cell carcinoma by inhibiting P53-mediated autophagy.

IF 4.8 2区医学 Q2 CELL BIOLOGY

Cellular Oncology Pub Date : 2025-08-01 Epub Date: 2025-05-06 DOI:10.1007/s13402-025-01065-6

Nan-Nan Ji, Shu-Ning Li, Ling Shao, Qing Li, Jun-Nv Xu, Yue-Can Zeng

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引用次数: 0

Abstract

Objective: Radioresistance is a common cause of poor radiation therapy effectiveness for non-small cell lung cancer. Finding molecular targets or methods to enhance radiosensitivity or overcome radioresistance is crucial. This study aimed to investigate the effects of MDMX on modulating radiosensitivity in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).

Methods: The expression of MDMX and its correlation with radiotherapy response were analyzed in 101 LUAD and LUSC patient samples. LUAD and LUSC cell lines (A549, SK-MES-1) and their radioresistant counterparts (A549R, SK-MES-1R) were used to assess the effects of MDMX and P53 on radiosensitivity through autophagy by using molecular assays and animal models.

Results: The expression of MDMX was decreased, but the autophagy was enhanced in radioresistant LUAD and LUSC cells. Overexpression of MDMX inhibited P53 activity, leading to autophagy suppression and increasing radiosensitivity. In contrast, P53 upregulation counteracted the effects of MDMX, resulting in increasing autophagy and radioresistance. The higher MDMX expression was associated with improved radiotherapy response and prolonged overall survival in LUAD and LUSC cells. The 5-year survival rate was 93.62% in the low MDMX expression group and 98.11% in the high MDMX expression group (P < 0.01).

Conclusion: MDMX enhances LUAD and LUSC radiosensitivity by downregulating P53-mediated autophagy. High MDMX expression correlated with better clinical outcomes, suggesting that MDMX could be a potential biomarker for predicting radiotherapy response and prognosis in LUAD and LUSC patients.

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MDMX通过抑制p53介导的自噬增强肺腺癌和鳞状细胞癌的放射敏感性。

目的：放疗耐药是导致非小细胞肺癌放疗效果不佳的常见原因。寻找分子靶点或方法来增强辐射敏感性或克服辐射抗性至关重要。本研究旨在探讨MDMX对肺腺癌（LUAD）和鳞状细胞癌（LUSC）放射敏感性的调节作用。方法：分析101例LUAD和LUSC患者MDMX的表达及其与放疗疗效的相关性。采用分子实验和动物模型，研究了MDMX和P53对LUAD和LUSC细胞株（A549、SK-MES-1）及其耐辐射细胞株（A549R、SK-MES-1R）通过自噬作用对放射敏感性的影响。结果：放射耐药LUAD和LUSC细胞中MDMX表达降低，自噬增强。MDMX过表达抑制P53活性，导致自噬抑制和放射敏感性增加。相反，P53上调抵消了MDMX的作用，导致自噬和放射耐药增加。在LUAD和LUSC细胞中，较高的MDMX表达与改善的放疗反应和延长的总生存期有关。MDMX低表达组5年生存率为93.62%，高表达组5年生存率为98.11% (P结论：MDMX通过下调p53介导的自噬增强LUAD和LUSC的放射敏感性。MDMX高表达与更好的临床结果相关，提示MDMX可能是预测LUAD和LUSC患者放疗反应和预后的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular Oncology ONCOLOGY-CELL BIOLOGY

CiteScore

10.30

自引率

1.50%

发文量

审稿时长

12 months

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.