Epigenetic modification of cuproptosis by non-coding RNAs in cancer drug resistance

IF 33.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2025-09-25 DOI:10.1186/s12943-025-02434-3

Fei Du, Lu Tang, Fang Wang, Xian Jiang, Junxin Li, Guojun Wang, Zhuo Zhang

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Abstract

Tumor drug resistance remains a significant barrier to effective cancer treatment, undermining the clinical efficacy of current therapies through adaptive and evolving mechanisms. Cuproptosis, a recently discovered form of programmed cell death, emerges as a promising tumor suppressor by targeting mitochondrial metabolic pathways, offering a novel strategy to combat drug resistance. However, targeting mitochondrial metabolism presents challenges due to the essential physiological roles of mitochondria in normal tissues, raising concerns about potential on-target toxicity. Recent studies have revealed the dynamic role of non-coding RNAs (ncRNAs) in modulating susceptibility to cuproptosis via epigenetic alterations, potentially serving as key factors in therapeutic response. In this review, we first summarize the complex interplay between chemotherapeutic resistance and cancer progression/relapse. Then, we outline the key molecular mechanisms underlying cuproptosis, its upstream epigenetic regulators, and the downstream effects on drug resistance. Finally, this review discusses the latest findings on how ncRNAs influence resistance to chemotherapy, immunotherapy, and targeted therapy by modulating cuproptosis. This review aims to untangle the regulatory mechanisms of ncRNA-mediated epigenetic modifications on cuproptosis, highlighting the critical role of the ncRNA-cuproptosis interaction network in tumor drug resistance progression. These insights provide a conceptual foundation for developing ncRNA-targeted therapies in conjunction with cuproptosis-inducing approaches.

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非编码rna在癌症耐药中的表观遗传修饰

肿瘤耐药仍然是有效治疗癌症的一个重要障碍，通过适应性和进化机制破坏了当前治疗的临床疗效。cuprotosis是最近发现的一种程序性细胞死亡形式，它通过靶向线粒体代谢途径成为一种有前途的肿瘤抑制因子，为对抗耐药性提供了一种新的策略。然而，由于线粒体在正常组织中的重要生理作用，靶向线粒体代谢提出了挑战，引起了对潜在靶毒性的担忧。最近的研究揭示了非编码rna （ncRNAs）在通过表观遗传改变调节铜体畸形易感性中的动态作用，可能是治疗反应的关键因素。在这篇综述中，我们首先总结了化疗耐药与癌症进展/复发之间的复杂相互作用。然后，我们概述了铜突起的关键分子机制，其上游表观遗传调控因子，以及下游对耐药的影响。最后，本综述讨论了ncRNAs如何通过调节cuprotosis影响化疗、免疫治疗和靶向治疗的耐药的最新发现。本文旨在阐明ncrna介导的表观遗传修饰对cuprotosis的调控机制，强调ncrna - cuprotosis相互作用网络在肿瘤耐药进展中的关键作用。这些见解为开发ncrna靶向治疗与铜体诱导方法相结合提供了概念基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.