Abnormally Expressed Ferroptosis-Associated FANCD2 in Mediating the Temozolomide Resistance and Immune Response in Glioblastoma

Song, Liying; Wu, Jiali; Fu, Hua; Wu, Cuifang; Tong, Xiaopei; Zhang, Mingyu

doi:10.3389/fphar.2022.921963

Cited by 7 publications

(7 citation statements)

References 39 publications

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“…Shi et al have found that Tirapazamine could induce ferroptosis by inhibiting SLC7A11 to inhibit the proliferation and migration of osteosarcoma cells [ 27 ]. Furthermore, high expression of FANCD2 can promote temozolomide resistance in glioblastoma cells by attenuating ferroptosis, while FANCD2 knockdown increases the levels of ROS and inhibits cell survival [ 7 ]. Based on previous studies, we speculated that FANCD2 may regulate osteosarcoma progression by mediating ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Fanconi anemia complementation group D2 (FANCD2) is involved in the regulation of tumorigenesis, apoptosis, and other life processes in cancers [ 6 ], such as glioblastoma [ 7 ], esophageal squamous cell carcinoma (ESCC) [ 8 ], and lung adenocarcinoma [ 9 ]. Elevated FANCD2 expression is correlated with a poor prognosis in primary and recurrent glioblastoma, silencing of FANCD2 inhibits cell survival [ 7 ]. Inhibition of FANCD2 distinctly inhibits cell proliferation, metastasis, and cell cycle progression in ESCC [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, in bone marrow stromal cells, FANCD2 involves in the regulation of genes associated with iron metabolism (such as FTH1 and TFRC) and lipid peroxidation (such as GPX4) [ 13 ]. FANCD2 promotes temozolomide resistance by slowing ferroptosis in glioblastoma cells [ 7 ]. However, the role of FANCD2 in regulating ferroptosis of osteosarcoma cells remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma

Liu

2023

BMC Cancer

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Background This research aimed to investigate the roles of fanconi anemia complementation group D2 (FANCD2) on the regulation of ferroptosis in osteosarcoma progression. Methods The function of FANCD2 on cell viability, invasion, migration, and tumor growth were explored. FANCD2 and pathway-related genes were determined by western blot. Ferroptosis-associated markers were determined, including lipid peroxidation, labile iron pool (LIP), ferrous iron (Fe2+), and ferroptosis-related genes. Results FANCD2 expression was increased in osteosarcoma cells. FANCD2 knockdown reduced cell viability, invasion, and migration of osteosarcoma cells. FANCD2 knockdown regulated ferroptosis-related gene expression, and distinctly increased the levels of LIP, Fe2+, and lipid peroxidation, and these effects were reversed by a ferroptosis inhibitor Fer-1. In addition, JAK2 and STAT3 expression were reduced by silencing of FANCD2, and STAT3 activator (colivelin) distinctly reversed tumor suppressor effects of FANCD2 silencing on osteosarcoma development. Conclusion These findings suggested that FANCD2 silencing could suppress osteosarcoma cell viability, migration, invasion, and tumor growth, and induced ferroptosis by regulating the JAK2/STAT3 axis. These findings may provide novel therapeutic ideas for clinical treatment of osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma

Liu

2023

BMC Cancer

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“…FANCD2 was found to involve in DNA inter-strand crosslinks repair upon stress and inhibit ferroptosis by regulating genes and/or proteins related to iron accumulation and lipid peroxidation ( 41 ). In glioblastoma, the expression FANCD2 was confirmed to promote drug resistance through attenuating ferroptosis while the inhibition of FNACD2 increased the ROS level and suppress cell survival ( 42 ). We observed the significant correlation of ZNF419 and FANCD2 among PRAD, BLCA, KIRC, LIHC, LUSC and STES, especially for PRAD, KIRC and LIHC.…”

Section: Discussionmentioning

confidence: 99%

A pan-cancer analysis of the oncogenic role of zinc finger protein 419 in human cancer

et al. 2022

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BackgroundAs a ferroptosis-related gene, the polymorphism of zinc finger protein 419 (ZNF419) at the splice donor site may generate renal cell carcinoma-associated novel minor histocompatibility antigen ZAPHIR. However, the role of ZNF419 in prognosis and immunology in human tumors remains largely unknown. This study aimed to visualize the prognostic landscape of ZNF419 at pan-cancer level and explore the relationship between ZNF419 expression and the tumor immune microenvironment.MethodPan-cancer and mutation data were downloaded from TCGA databases and analyzed through R (version 3.6.4) and its suitable packages. Differential ZNF419 expression and prognosis were analyzed. Correlations with ferroptosis-related genes, pathway analysis, tumor stemness, heterogeneity, mutation landscape, and RNA modifications were also explored. The relationships between ZNF419 expression and tumor immunity were investigated through the TIMER and ESTIMATE methods.ResultZNF419 was differentially expressed between tumor and normal samples and was associated with overall survival, disease-specific survival and progression-free interval for STES, KIRC, LIHC, LUSC, PRAD, and BLCA. We found the interaction between ZNF419 and FANCD2 might involve in ferroptosis in pan-cancer level. In addition, the mutation frequencies of STES, KIRC, LIHC, LUSC, PRAD, and BLCA were 1.5%, 0.3%, 0.3%, 1.9%, 0.2%, and 0.7%, respectively. We detected that the expression of ZNF419 was closely correlated with most immune checkpoint genes and immune regulatory genes. Furthermore, we found that the ZNF419 expression level was negatively related to the immune score in the six cancers mentioned above. The expression of ZNF419 was significantly associated with various infiltrating immune cells, such as CD4+ T cells, CD8+ T cells, and macrophages in patients with KIRC, PRAD, and LUSC but was only significantly related to macrophages in BLCA patients.ConclusionZNF419 might serve as a potential prognostic and immunological pan-cancer biomarker, especially for KIRC, LIHC, LUSC, PRAD, and BLCA.

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“…The p53-NRF2 association and p53-mediated inhibition of NRF2 antioxidant activity are regulated by p62 according to the state of p53 ( Zhang et al, 2020d ). The dual regulation of ferroptosis by p62 requires the P53 mutational status ( Jankowski and Rabinowitz, 2022 ; Song et al, 2022 ). In the p53-wild-type GBM, the classical p62-mediated NRF2 activation pathway plays a major role in regulating iron cell apoptosis, thus leading to increased SLC7A11 expression and acting as an anti-iron cell apoptosis mechanism ( Ma et al, 2020 ).…”

Section: Ferroptosis In Glioblastomamentioning

confidence: 99%

Molecular mechanisms of ferroptosis and the potential therapeutic targets of ferroptosis signaling pathways for glioblastoma

et al. 2022

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Ferroptosis is a newly identified form of cell death that differs from autophagy, apoptosis and necrosis, and its molecular characteristics include iron-dependent lipid reactive oxygen species accumulation, mitochondrial morphology changes, and membrane permeability damage. These characteristics are closely related to various human diseases, especially tumors of the nervous system. Glioblastoma is the most common primary malignant tumor of the adult central nervous system, and the 5-year survival rate is only 4%–5%. This study reviewed the role and mechanism of ferroptosis in glioblastoma and the research status and progress on ferroptosis as a potential therapeutic target. The mechanism of ferroptosis is related to the intracellular iron metabolism level, lipid peroxide content and glutathione peroxidase 4 activity. It is worth exploring how ferroptosis can be applied in disease treatment; however, the relation between ferroptosis and other apoptosis methods is poorly understood and methods of applying ferroptosis to drug-resistant tumors are insufficient. Ferroptosis is a promising therapeutic target for glioblastoma. In-depth studies of its mechanism of action in glioblastoma and applications for clinical treatment are expected to provide insights for glioblastoma patients.

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Abnormally Expressed Ferroptosis-Associated FANCD2 in Mediating the Temozolomide Resistance and Immune Response in Glioblastoma

Cited by 7 publications

References 39 publications

FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma

FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma

A pan-cancer analysis of the oncogenic role of zinc finger protein 419 in human cancer

Molecular mechanisms of ferroptosis and the potential therapeutic targets of ferroptosis signaling pathways for glioblastoma

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