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RNA m6A 修饰在铁死亡中的作用:对推进肿瘤免疫治疗的启示。

RNA m6A modification in ferroptosis: implications for advancing tumor immunotherapy.

机构信息

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China.

The Department of Medical Genetics, Naval Medical University, Shanghai, 200433, China.

出版信息

Mol Cancer. 2024 Sep 28;23(1):213. doi: 10.1186/s12943-024-02132-6.


DOI:10.1186/s12943-024-02132-6
PMID:39342168
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11437708/
Abstract

The pursuit of innovative therapeutic strategies in oncology remains imperative, given the persistent global impact of cancer as a leading cause of mortality. Immunotherapy is regarded as one of the most promising techniques for systemic cancer therapies among the several therapeutic options available. Nevertheless, limited immune response rates and immune resistance urge us on an augmentation for therapeutic efficacy rather than sticking to conventional approaches. Ferroptosis, a novel reprogrammed cell death, is tightly correlated with the tumor immune environment and interferes with cancer progression. Highly mutant or metastasis-prone tumor cells are more susceptible to iron-dependent nonapoptotic cell death. Consequently, ferroptosis-induction therapies hold the promise of overcoming resistance to conventional treatments. The most prevalent post-transcriptional modification, RNA m6A modification, regulates the metabolic processes of targeted RNAs and is involved in numerous physiological and pathological processes. Aberrant m6A modification influences cell susceptibility to ferroptosis, as well as the expression of immune checkpoints. Clarifying the regulation of m6A modification on ferroptosis and its significance in tumor cell response will provide a distinct method for finding potential targets to enhance the effectiveness of immunotherapy. In this review, we comprehensively summarized regulatory characteristics of RNA m6A modification on ferroptosis and discussed the role of RNA m6A-mediated ferroptosis on immunotherapy, aiming to enhance the effectiveness of ferroptosis-sensitive immunotherapy as a treatment for immune-resistant malignancies.

摘要

鉴于癌症作为主要死亡原因在全球范围内的持续影响,在肿瘤学中追求创新的治疗策略仍然是当务之急。免疫疗法被认为是几种治疗选择中用于全身癌症治疗最有前途的技术之一。然而,有限的免疫反应率和免疫抵抗促使我们增强治疗效果,而不是坚持传统方法。铁死亡是一种新的重编程细胞死亡,与肿瘤免疫环境密切相关,并干扰癌症进展。高度突变或易转移的肿瘤细胞更容易受到铁依赖性非凋亡细胞死亡的影响。因此,诱导铁死亡的治疗方法有望克服对传统治疗的抵抗。最常见的转录后修饰,RNA m6A 修饰,调节靶向 RNA 的代谢过程,并参与许多生理和病理过程。异常的 m6A 修饰影响细胞对铁死亡的敏感性,以及免疫检查点的表达。阐明 m6A 修饰对铁死亡的调节及其在肿瘤细胞反应中的意义将为寻找增强免疫疗法效果的潜在靶点提供一种独特的方法。在这篇综述中,我们全面总结了 RNA m6A 修饰对铁死亡的调控特征,并讨论了 RNA m6A 介导的铁死亡在免疫治疗中的作用,旨在增强铁死亡敏感免疫治疗作为治疗免疫抵抗性恶性肿瘤的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/4a647a63fd21/12943_2024_2132_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/79ac0ca81848/12943_2024_2132_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/30d221610521/12943_2024_2132_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/490b913c015e/12943_2024_2132_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/d781ace2357f/12943_2024_2132_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/4a647a63fd21/12943_2024_2132_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/79ac0ca81848/12943_2024_2132_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/30d221610521/12943_2024_2132_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/490b913c015e/12943_2024_2132_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/d781ace2357f/12943_2024_2132_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/453a/11437708/4a647a63fd21/12943_2024_2132_Fig5_HTML.jpg

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[2]
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[4]
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引用本文的文献

[1]
M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challenges.

Front Oncol. 2025-7-16

[2]
Emerging Therapeutic Strategies Targeting GPX4-Mediated Ferroptosis in Head and Neck Cancer.

Int J Mol Sci. 2025-7-4

[3]
Targeting ferroptosis: a promising avenue for ovarian cancer treatment.

Front Immunol. 2025-6-5

[4]
RBM15-mediated metabolic reprogramming boosts immune response in colorectal cancer.

Front Immunol. 2025-4-30

[5]
Identification of N6-methyladenosine-associated ferroptosis biomarkers in cervical cancer.

Hereditas. 2025-4-7

[6]
Multifunctional glycyrrhizic acid-loaded nanoplatform combining ferroptosis induction and HMGB1 blockade for enhanced tumor immunotherapy.

J Nanobiotechnology. 2025-3-19

[7]
The RNA Demethyltransferase FTO Regulates Ferroptosis in Major Depressive Disorder.

Int J Mol Sci. 2025-1-26

[8]
Correction: RNA m6A modification in ferroptosis: implications for advancing tumor immunotherapy.

Mol Cancer. 2024-10-8

本文引用的文献

[1]
METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma.

J Hematol Oncol. 2024-9-2

[2]
N6-methyladenosine writer METTL16-mediated alternative splicing and translation control are essential for murine spermatogenesis.

Genome Biol. 2024-7-19

[3]
The role of RNA methylation in tumor immunity and its potential in immunotherapy.

Mol Cancer. 2024-6-20

[4]
mA modification of lncRNA ABHD11-AS1 promotes colorectal cancer progression and inhibits ferroptosis through TRIM21/IGF2BP2/ FOXM1 positive feedback loop.

Cancer Lett. 2024-8-1

[5]
Profiling of mA methylation in porcine intramuscular adipocytes and unravelling PHKG1 represses porcine intramuscular lipid deposition in an mA-dependent manner.

Int J Biol Macromol. 2024-6

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METTL3 deficiency leads to ovarian insufficiency due to IL-1β overexpression in theca cells.

Free Radic Biol Med. 2024-9

[7]
METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs.

Int J Oral Sci. 2024-5-23

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Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice.

Nat Commun. 2024-5-21

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METTL14 decreases FTH1 mRNA stability via m6A methylation to promote sorafenib-induced ferroptosis of cervical cancer.

Cancer Biol Ther. 2024-12-31

[10]
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J Hematol Oncol. 2024-5-6

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