1. Pan-cancer analysis of the tumorigenic role of Fanconi anemia complementation group D2 (FANCD2) in human tumors.
- Author
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Xie, Xiaozhou, Zhao, Yulong, Du, Fengying, Cai, Baoshan, Fang, Zhen, Liu, Yuan, Sang, Yaodong, Ma, Chenghao, Liu, Zhaodong, Yu, Xinshuai, Zhang, Chi, Jiang, Jiayu, Gao, Zi, Liu, Yan, Lin, Xiaoyan, Jing, Haiyan, Zhong, Xiuming, Cong, Lei, Dai, Honghai, and Sha, Dan
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FANCONI'S anemia , *CANCER cell proliferation , *PROGRAMMED cell death 1 receptors , *IMMUNE checkpoint proteins , *TUMORS , *CELL cycle - Abstract
Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors. • This study provides the first pan-cancer analysis of FANCD2 using data from public databases. • FANCD2 is upregulated and has poor prognosis in most cancers and plays a potential role in regulating tumor immunity. • We further validated FANCD2 as an important oncogenic gene and promotes tumor progression by regulating cell cycle. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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