RAD18通过调节ATM/STAT3/PD-L1促进食管鳞状细胞癌的细胞恶性行为。
RAD18 promotes cell malignant behaviors of esophageal squamous cell carcinoma by modulating ATM/STAT3/PD-L1.
作者信息
Yang Xianghui, Song Qishi, Li Min, Liu Da
机构信息
Department of Oncology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha City, Hunan Province, China.
Interventional Treatment Room, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha City, Hunan Province, China.
出版信息
Chromosoma. 2025 Jul 9;134(1):6. doi: 10.1007/s00412-025-00832-6.
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.
背景
食管癌（EC）仍是医学上的难题，每年致使众多患者丧生。RAD18和ATM与包括食管鳞状细胞癌（ESCC）在内的多种癌症有关。然而，RAD18/ATM轴是否影响ESCC进展仍不清楚。
方法
使用RT-qPCR和蛋白质印迹法评估基因和蛋白质的丰度。使用克隆形成、划痕试验和Transwell检测细胞增殖、迁移和侵袭。使用免疫共沉淀验证并实验ATM泛素化水平。
结果
我们的研究结果发现，在TCGA数据库、ESCC患者和ESCC细胞中，RAD18表达增强。同样，ESCC患者和ESCC细胞中的ATM表达下降。RAD18沉默导致ESCC细胞的增殖、迁移和侵袭受到抑制，而ATM沉默可消除这些抑制作用。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敲低可逆转这种作用。而且，RAD18可降低ATM蛋白水平。
结论
RAD18介导ATM泛素化以降低ATM蛋白水平，从而激活STAT3/PD-L1轴并增强ESCC细胞的增殖、迁移和侵袭。
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