RAD18 promotes cell malignant behaviors of esophageal squamous cell carcinoma by modulating ATM/STAT3/PD-L1.

IF 2.5 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chromosoma Pub Date : 2025-07-09 DOI:10.1007/s00412-025-00832-6

Xianghui Yang, Qishi Song, Min Li, Da Liu

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引用次数: 0

Abstract

Background: Esophageal cancer (EC) is still a difficult problem in medicine, depriving many patients of their lives every year. RAD18 and ATM were implicated in cancers including esophageal squamous cell carcinoma (ESCC). However, whether RAD18/ATM axis influences ESCC progression remains unclear.

Methods: The abundance of genes and proteins was evaluated using RT-qPCR and western blot. Cell proliferation, migration and invasion were examined using clone formation, scratch test and transwell. The level of ATM ubiquitination was verified and experimented using Co-IP.

Results: Our findings found that RAD18 expression was enhanced in TCGA database, in ESCC patients and ESCC cells. Similarly, ATM expression was declined in ESCC patients and ESCC cells. RAD18 silencing resulted in suppression of cell proliferation, migration and invasion of ESCC cells, which were abolished by ATM silencing. In addition, ATM silencing promoted malignant behaviors of ESCC cells by activating STAT3/PD-L1 axis, which was reversed by PD-L1 knockdown. Moreover, RAD18 could reduce ATM protein levels.

Conclusion: RAD18 mediated ATM ubiquitination to reduce ATM protein level, thereby activating STAT3/PD-L1 axis and strengthening cell proliferation, migration and invasion of ESCC cells.

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RAD18通过调控ATM/STAT3/PD-L1促进食管鳞状细胞癌的细胞恶性行为。

背景：食管癌仍是医学难题，每年夺去许多患者的生命。RAD18和ATM与包括食管鳞状细胞癌（ESCC）在内的癌症有关。然而，RAD18/ATM轴是否影响ESCC进展尚不清楚。方法：采用RT-qPCR和western blot检测基因和蛋白的丰度。用克隆形成法、划痕法和transwell法检测细胞的增殖、迁移和侵袭。用Co-IP对ATM泛素化水平进行了验证和实验。结果：我们的研究发现，在TCGA数据库中，在ESCC患者和ESCC细胞中，RAD18的表达增强。同样，ATM在ESCC患者和ESCC细胞中的表达也下降。RAD18沉默可抑制ESCC细胞的增殖、迁移和侵袭，而ATM沉默可消除这些作用。此外，ATM沉默通过激活STAT3/PD-L1轴促进ESCC细胞的恶性行为，而PD-L1敲低可逆转这一过程。RAD18可以降低ATM蛋白水平。结论：RAD18介导ATM泛素化，降低ATM蛋白水平，从而激活STAT3/PD-L1轴，增强ESCC细胞的增殖、迁移和侵袭能力。

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

Chromosoma 生物-生化与分子生物学

CiteScore

3.30

自引率

6.20%

发文量

审稿时长

1 months

期刊介绍： Chromosoma publishes research and review articles on the functional organization of the eukaryotic cell nucleus, with a particular emphasis on the structure and dynamics of chromatin and chromosomes; the expression and replication of genomes; genome organization and evolution; the segregation of genomes during meiosis and mitosis; the function and dynamics of subnuclear compartments; the nuclear envelope and nucleocytoplasmic interactions, and more. The scope of Chromosoma encompasses genetic, biophysical, molecular and cell biological studies. Average time from receipt of contributions to first decision: 22 days Publishes research and review articles on the functional organization of the eukaryotic cell nucleus Topics include structure and dynamics of chromatin and chromosomes; the expression and replication of genomes; genome organization and evolution; the segregation of genomes during meiosis and mitosis and more Encompasses genetic, biophysical, molecular and cell biological studies.