PARPi treatment enhances radiotherapy-induced ferroptosis and antitumor immune responses via the cGAS signaling pathway in colorectal cancer

Shen, Dong-Ya; Luo, Jia; Chen, Ling; Ma, Wenjuan; Mao, Xiao‐Yuan; Zheng, Jinsen; Wang, Yang; Wan, Jielin; Wang, Shiyu; Ouyang, Jing; Yi, Hanyin; Liu, Dongbo; Huang, Wei‐Hua; Zhang, Wei; Liu, Zhao‐Qian; McLeod, Howard L.; He, Yijing

doi:10.1016/j.canlet.2022.215919

Cited by 43 publications

(22 citation statements)

References 37 publications

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“…Among the 19 DE‐FRGs, PARP3, PARP9, PARP10, PARP12, PARP14 are the members of poly ADP‐ribose polymerase (PARP) family, which are involved in DNA repair, DNA methylation, transcriptional regulation, and metabolic regulation 39 . Previous study has showed the role of PARP in promoting ferroptosis via regulating the expression of SLC7A11 in some diseases 40,41 . And many members of PARP family were found to be upregulated in FFA cases compared with healthy controls in this study.…”

Section: Discussionmentioning

confidence: 52%

Transcriptome analysis of frontal fibrosis alopecia revealed involvement of immune cells and ferroptosis

Liu,

Xue,

Wang

et al. 2024

Skin Research and Technology

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BackgroundFrontal fibrosis alopecia (FFA) is a primary cicatricial alopecia and has received increasing attention in recent years. However, the pathogenesis of FFA has not been fully elucidated.Methods and resultsHerein, we collected the transcriptome data of scalp lesions of seven patients with FFA and seven healthy controls. The differential expression analysis and weighted gene co‐expression network analysis were conducted and we identified 458 differentially expressed genes (DEGs) in two key modules. Later, we performed functional enrichment analysis and functional modules identification, revealing the participation of immune response and fatty acid metabolism. Based on the results, we processed further studies. On the one hand, we analyzed the infiltrating immune cells of FFA through CIBERSORT algorithm, indicating the activation of M1 macrophage and CD8+ T cell. On the other hand, considering lipid metabolism of FFA and oxidative stress of hair follicle cells in alopecia, we explored the potential ferroptosis of FFA. By intersection of DEGs and ferroptosis‐related genes from FerrDb database, 19 genes were identified and their expression was validated in an external dataset containing 36 FFA cases and 12 controls. Then, we used LASSO algorithms to construct a four‐gene diagnostic model, which achieved an AUC of 0.924 in validation dataset. Additionally, the immune cells were found to be related to ferroptosis in FFA.ConclusionTaken together, this study contributed to reveal the molecular mechanisms of FFA and is expected to inspire future research on treatment.

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Section: Discussionmentioning

confidence: 52%

Transcriptome analysis of frontal fibrosis alopecia revealed involvement of immune cells and ferroptosis

Liu,

Xue,

Wang

et al. 2024

Skin Research and Technology

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“…Increasing evidence further postulates that ferroptosis is an important form of IRinduced cell death [42,43]. Shen DY et al [44] strongly suggested that ferroptosis plays a major role in IRinduced cell death. Mechanistically, IR induces the production of ROS and iron overload, resulting in increased lipid peroxidation and ferroptosis [22].…”

Section: Discussionmentioning

confidence: 99%

Perillaldehyde mitigates ionizing radiation-induced intestinal injury by inhibiting ferroptosis via the Nrf2 signaling pathway

Tang¹,

Xie

Zhou³

et al. 2023

Preprint

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The gastrointestinal tract is a rapidly self-renewing system and is thus highly sensitive to ionizing radiation (IR). Unfortunately, methods for preventing and treating IR-induced gastrointestinal syndrome are limited. Volatile monoterpenoid perillaldehyde (PAH) is the major component of the essential oil extracted from perilla plants and has been demonstrated to have antioxidant, anti-inflammatory, antimicrobial activity, and antitumor effects. However, its role in preventing or alleviating radiation-induced injuries remains unknown. In this study, PAH prolonged the survival time and attenuated radiation-induced intestinal injury in whole abdominal lethally irradiated mice. PAH treatment also promoted the survival of crypt cells, attenuated radiation-induced DNA damage, and mitigated intestinal barrier damage in irradiated mice. The radioprotective effects of PAH in intestinal crypt organoids and human intestinal epithelial cell line (HIEC-6) were also identified. PAH-mediated radioprotection was associated with the upregulation of Nrf2, activation of the antioxidant pathway, and inhibition of ferroptosis. Notably, treatment with the Nrf2 inhibitor ML385 abolished the protective effects of PAH, indicating that Nrf2 activation is essential for PAH activity. The findings of this study collectively suggest that PAH is a promising therapeutic strategy for IR-induced intestinal injury.

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“…Recently, the effects of ferroptosis in radiotherapy have attracted much interest. Previous investigations highlighted the fatal consequences of lipid peroxides introduced by ferroptosis and irradiation, as well as the synergistic effect of ferroptosis on radiotherapy [ 4 , 6 , 25 ]. According to some research, amino acids may influence tumor response to irradiation via modulating ferroptosis signals [ 6 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Glutamine Transporter SLC1A5 Regulates Ionizing Radiation-Derived Oxidative Damage and Ferroptosis

Yuan

Liu

Huo

et al. 2022

Oxidative Medicine and Cellular Longevity

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Ionizing radiation-derived oxidative stress and ferroptosis are one of the most important biological effects on destroying the liver tumor, whereas radioresistance of liver tumor remains a leading cause of radiotherapy (RT) failure mainly because of the protective antiferroptosis, in which oxidative stress and subsequent lipid peroxidation are the key initiators. Thus, it is of great importance to overcome ferroptosis resistance to improve the therapeutic efficacy of RT in liver tumor patients. Irradiation-resistant HepG2 cells (HepG2-IRR) were established by long-term exposure to X-ray (2 to 8 Gy), and targeted metabolomics analysis revealed an obvious increase in intracellular amino acids in HepG2-IRR cells upon ferroptosis stress. Among these amino acids with obvious changes, N-acetylglutamine, a derivative of glutamine, is essential for the redox homeostasis and progression of tumor cells. Interestingly, the treatment of glutamine starvation could promote the ferroptosis effect significantly, whereas glutamine supplementation reversed the ferroptosis effect completely. Consistent with the changes in amino acids pattern, the glutamine transporter SLC1A5 was verified in liver tumor samples from TCGA training and validation cohorts as an independent prognostic amino acid-ferroptosis gene (AFG). A risk score for screening prognosis based on the SLC1A5, SLC7A11, ASNS, and TXNRD1 demonstrated that a high-risk score was correlated with poor survival. In vitro studies had shown that the knockdown of SLC1A5 resulted in a significant decrease in cell viability and promoted lipid peroxidation and oxidative damage introduced by irradiation (10 Gy). Collectively, our findings indicated that SLC1A5 may act as a suppressor gene against ferroptosis and can be a potential target for ionizing radiation mediated effects.

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PARPi treatment enhances radiotherapy-induced ferroptosis and antitumor immune responses via the cGAS signaling pathway in colorectal cancer

Cited by 43 publications

References 37 publications

Transcriptome analysis of frontal fibrosis alopecia revealed involvement of immune cells and ferroptosis

Transcriptome analysis of frontal fibrosis alopecia revealed involvement of immune cells and ferroptosis

Perillaldehyde mitigates ionizing radiation-induced intestinal injury by inhibiting ferroptosis via the Nrf2 signaling pathway

Glutamine Transporter SLC1A5 Regulates Ionizing Radiation-Derived Oxidative Damage and Ferroptosis

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