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胃肠道癌症中铁死亡的表观遗传调控(综述)

Epigenetic regulation of ferroptosis in gastrointestinal cancers (Review).

作者信息

Gong Linqiang, Wu Linlin, Zhao Shiyuan, Xiao Shuai, Chu Xue, Zhang Yazhou, Li Fengfeng, Li Shuhui, Yang Hui, Jiang Pei

机构信息

Department of Gastroenterology, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China.

Oncology Department, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China.

出版信息

Int J Mol Med. 2025 Jun;55(6). doi: 10.3892/ijmm.2025.5534. Epub 2025 Apr 17.


DOI:10.3892/ijmm.2025.5534
PMID:40242977
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12045471/
Abstract

Ferroptosis is a type of iron‑dependent cell death characterized by excessive lipid peroxidation and may serve as a potential therapeutic target in cancer treatment. While the mechanisms governing ferroptosis continue to be explored and elucidated, an increasing body of research highlights the significant impact of epigenetic modifications on the sensitivity of cancer cells to ferroptosis. Epigenetic processes, such as DNA methylation, histone modifications and non‑coding RNAs, have been identified as key regulators that modulate the expression of ferroptosis‑related genes. These alterations can either enhance or inhibit the sensitivity of gastrointestinal cancer (GIC) cells to ferroptosis, thereby affecting the fate of GICs. Drugs that target epigenetic markers for advanced‑stage cancer have shown promising results in enhancing ferroptosis and inhibiting tumor growth. This review explores the intricate relationship between epigenetic regulation and ferroptosis in GICs. Additionally, the potential of leveraging epigenetic modifications to trigger ferroptosis in GICs is investigated. This review highlights the importance of further research to elucidate the specific mechanisms underlying epigenetic control of ferroptosis and to advance the development of novel therapeutic approaches.

摘要

铁死亡是一种铁依赖性细胞死亡,其特征是脂质过氧化过度,可能是癌症治疗中的一个潜在治疗靶点。虽然铁死亡的调控机制仍在不断探索和阐明,但越来越多的研究强调了表观遗传修饰对癌细胞铁死亡敏感性的重大影响。表观遗传过程,如DNA甲基化、组蛋白修饰和非编码RNA,已被确定为调节铁死亡相关基因表达的关键调节因子。这些改变可增强或抑制胃肠道癌细胞(GIC)对铁死亡的敏感性,从而影响GIC的命运。针对晚期癌症表观遗传标记的药物在增强铁死亡和抑制肿瘤生长方面已显示出有前景的结果。本综述探讨了GIC中表观遗传调控与铁死亡之间的复杂关系。此外,还研究了利用表观遗传修饰在GIC中引发铁死亡的潜力。本综述强调了进一步研究以阐明铁死亡表观遗传控制的具体机制并推动新型治疗方法发展的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab05/12045471/951c90555535/ijmm-55-06-05534-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab05/12045471/cbb0f60f92ed/ijmm-55-06-05534-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab05/12045471/866d8b5ae8ec/ijmm-55-06-05534-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab05/12045471/951c90555535/ijmm-55-06-05534-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab05/12045471/cbb0f60f92ed/ijmm-55-06-05534-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab05/12045471/866d8b5ae8ec/ijmm-55-06-05534-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab05/12045471/951c90555535/ijmm-55-06-05534-g02.jpg

相似文献

[1]
Epigenetic regulation of ferroptosis in gastrointestinal cancers (Review).

Int J Mol Med. 2025-6

[2]
Ferroptosis in Cancer: Epigenetic Control and Therapeutic Opportunities.

Biomolecules. 2024-11-13

[3]
Epigenetic regulation of autophagy in gastrointestinal cancers.

Biochim Biophys Acta Mol Basis Dis. 2022-11-1

[4]
Epigenetic modulation of ferroptosis in cancer: Identifying epigenetic targets for novel anticancer therapy.

Cell Oncol (Dordr). 2023-12

[5]
Alteration in DNA methylation patterns: Epigenetic signatures in gastrointestinal cancers.

Eur J Pharmacol. 2024-6-15

[6]
Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases.

Signal Transduct Target Ther. 2023-12-10

[7]
Non‑coding RNA‑mediated epigenetic modification of ferroptosis in non‑small cell lung cancer (Review).

Int J Oncol. 2025-1

[8]
Epigenetic modification of ferroptosis by non-coding RNAs in cancer drug resistance.

Mol Cancer. 2024-8-27

[9]
The Role of Methylation in Ferroptosis.

J Cardiovasc Transl Res. 2024-12

[10]
Epigenetic and post-translational modifications in ferroptosis regulation and hepatocellular carcinoma: New frontiers in therapeutic targeting.

Pathol Res Pract. 2025-6

本文引用的文献

[1]
Lactylation of HDAC1 Confers Resistance to Ferroptosis in Colorectal Cancer.

Adv Sci (Weinh). 2025-3

[2]
5-methylcytosine methylation of MALAT1 promotes resistance to sorafenib in hepatocellular carcinoma through ELAVL1/SLC7A11-mediated ferroptosis.

Drug Resist Updat. 2025-1

[3]
Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial.

Nat Commun. 2024-11-12

[4]
Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics.

Nat Rev Mol Cell Biol. 2025-1

[5]
IDH1 Inhibition Potentiates Chemotherapy Efficacy in Pancreatic Cancer.

Cancer Res. 2024-9-16

[6]
CRISPR-Cas9 library screening combined with an exosome-targeted delivery system addresses tumorigenesis/TMZ resistance in the mesenchymal subtype of glioblastoma.

Theranostics. 2024

[7]
HDAC inhibitors activate lipid peroxidation and ferroptosis in gastric cancer.

Biochem Pharmacol. 2024-7

[8]
Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis.

J Hematol Oncol. 2024-4-23

[9]
EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2.

Cancer Sci. 2024-7

[10]
Gastric cancer secreted miR-214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells.

Oncol Res. 2024

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