Ferroptosis triggered by STAT1- IRF1-ACSL4 pathway was involved in radiation-induced intestinal injury

Kong, Peizhong; Yang, Miaomiao; Wang, Ying; Yu, K.N.; Wu, Lijun; Han, Wei

doi:10.1016/j.redox.2023.102857

Cited by 24 publications

(7 citation statements)

References 45 publications

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“…We mimicked oxidative stress in vitro by treating HCC cells with H 2 O 2 . MDA is an important marker for lipid peroxidation [ 50 , 51 ]. SOD is an antioxidant enzyme capable of scavenging superoxide anion radicals generated within cells, thereby protecting cells from oxidative damage [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect hepatocellular carcinoma cells from oxidative stress

Liu,

Dou,

Cao

2024

BMC Gastroenterol

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Background Cellular response to oxidative stress plays significant roles in hepatocellular carcinoma (HCC) development, yet the exact mechanism by which HCC cells respond to oxidative stress remains poorly understood. This study aimed to investigate the role and mechanism of super enhancer (SE)-controlled genes in oxidative stress response of HCC cells. Methods The GSE112221 dataset was used to identify SEs by HOMER. Functional enrichment of SE-controlled genes was performed by Metascape. Transcription factors were predicted using HOMER. Prognosis analysis was conducted using the Kaplan-Meier Plotter website. Expression correlation analysis was performed using the Tumor Immune Estimation Resource web server. NRF1 and SPIDR expression in HCC and normal liver tissues was analyzed based on the TCGA-LIHC dataset. ChIP-qPCR was used to detect acetylation of lysine 27 on histone 3 (H3K27ac) levels of SE regions of genes, and the binding of NRF1 to the SE of SPIDR. To mimic oxidative stress, HepG2 and Hep3B cells were stimulated with H2O2. The effects of NRF1 and SPIDR on the oxidative stress response of HCC cells were determined by the functional assays. Results A total of 318 HCC-specific SE-controlled genes were identified. The functions of these genes was significant association with oxidative stress response. SPIDR and RHOB were enriched in the “response to oxidative stress” term and were chosen for validation. SE regions of SPIDR and RHOB exhibited strong H3K27ac modification, which was significantly inhibited by JQ1. JQ1 treatment suppressed the expression of SPIDR and RHOB, and increased reactive oxygen species (ROS) levels in HCC cells. TEAD2, TEAD3, NRF1, HINFP and TCFL5 were identified as potential transcription factors for HCC-specific SE-controlled genes related to oxidative stress response. The five transcription factors were positively correlated with SPIDR expression, with the highest correlation coefficient for NRF1. NRF1 and SPIDR expression was up-regulated in HCC tissues and cells. NRF1 activated SPIDR transcription by binding to its SE. Silencing SPIDR or NRF1 significantly promoted ROS accumulation in HCC cells. Under oxidative stress, silencing SPIDR or NRF1 increased ROS, malondialdehyde (MDA) and γH2AX levels, and decreased superoxide dismutase (SOD) levels and cell proliferation of HCC cells. Furthermore, overexpression of SPIDR partially offset the effects of NRF1 silencing on ROS, MDA, SOD, γH2AX levels and cell proliferation of HCC cells. Conclusion NRF1 driven SPIDR transcription by occupying its SE, protecting HCC cells from oxidative stress-induced damage. NRF1 and SPIDR are promising biomarkers for targeting oxidative stress in the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect hepatocellular carcinoma cells from oxidative stress

Liu,

Dou,

Cao

2024

BMC Gastroenterol

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“…Recently, ferroptosis of intestinal epithelial cells has been confirmed to be a promoting factor in the development of intestinal fibrosis. [ 157 ] Specifically, STAT1-IRF1-ACSL4 axis-dependent ferroptosis was found to be an important mechanism in the process of interstitial fibrosis induced by radiation. [ 157 ] Regretfully, current studies assessing the relationship between ferroptosis and interstitial fibrosis are very limited, and there remains a lot of room for further research.…”

Section: Ferroptosis and Other Fibrotic Organsmentioning

confidence: 99%

Ferroptosis in organ fibrosis: From mechanisms to therapeutic medicines

Lai,

Wang,

Huang

et al. 2024

Journal of Translational Internal Medicine

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Fibrosis occurs in many organs, and its sustained progress can lead to organ destruction and malfunction. Although numerous studies on organ fibrosis have been carried out, its underlying mechanism is largely unknown, and no ideal treatment is currently available. Ferroptosis is an iron-dependent process of programmed cell death that is characterized by lipid peroxidation. In the past decade, a growing body of evidence demonstrated the association between ferroptosis and fibrotic diseases, while targeting ferroptosis may serve as a potential therapeutic strategy. This review highlights recent advances in the crosstalk between ferroptosis and organ fibrosis, and discusses ferroptosis-targeted therapeutic approaches against fibrosis that are currently being explored.

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“…More research predominantly focuses on radiation-induced intestinal injury 77 - 80 . Similarly, investigations on IR-induced ferroptosis in radiation injury have primarily concentrated on intestinal injury 81 - 84 , lung injury 85 - 88 , with limited studies on hematopoietic system injury 89 , 90 , wound repair 91 , hippocampus neurons injury 92 , and skin injury 93 . Research on radiation-induced necroptosis in the field of radiation injury primarily focuses on lung injury 94 and intestinal injury 95 .…”

Section: Introductionmentioning

confidence: 99%

“…IR stimulates the STAT1/interferon regulatory factor (IRF1)/ACSL4 signaling pathway and nuclear receptor coactivator 4 (NCOA4)-induced ferritinophagy, leading to intracellular iron overload and ferroptosis. Ferrostatin-1 and the DFO effectively attenuate iron metabolism, thereby alleviating radiation-induced intestinal injury 81 , 82 . Additionally, Li et al reported that ferrostatin-1 enhances radiation sensitivity while reducing radiation-induced intestinal injury 120 .…”

Section: Introductionmentioning

confidence: 99%

The scheme, and regulative mechanism of pyroptosis, ferroptosis, and necroptosis in radiation injury

Ning,

Chen,

Zeng

et al. 2024

Int. J. Biol. Sci.

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Radiotherapy (RT) stands as the primary treatment for tumors, but it inevitably causes damage to normal cells. Consequently, radiation injury is a crucial consideration for radiation oncologists during therapy planning. Cell death including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis play significant roles in tumor treatment. While previous studies elucidated the induction of apoptosis and autophagy by ionizing radiation (IR), recent attention has shifted to pyroptosis, ferroptosis, and necroptosis, revealing their effects induced by IR. This review aims to summarize the strategies employed by IR, either alone or in combination therapy, to induce pyroptosis, ferroptosis, and necroptosis in radiation injury. Furthermore, we explore their effects and molecular pathways, shedding light on their roles in radiation injury. Finally, we summarize the regulative agents for these three types of cell death and their mechanisms. In summary, optimizing radiation dose, dose rate, and combined treatment plans to minimize radiation damage and enhance the killing effect of RT is a key focus.

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Ferroptosis triggered by STAT1- IRF1-ACSL4 pathway was involved in radiation-induced intestinal injury

Cited by 24 publications

References 45 publications

Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect hepatocellular carcinoma cells from oxidative stress

Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect hepatocellular carcinoma cells from oxidative stress

Ferroptosis in organ fibrosis: From mechanisms to therapeutic medicines

The scheme, and regulative mechanism of pyroptosis, ferroptosis, and necroptosis in radiation injury

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