Journal Article

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

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

2025

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Animals / Antigen presentation / Antimitotic agents / Antineoplastic agents / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Apoptosis / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cancer therapies / Cell cycle / Cell death / Cell Death Mechanisms in Cancer / Chemoresistance / Chemotherapy / Copper / Cuproptosis / Development and progression / DNA methylation / DNA repair / Drug resistance / Drug Resistance, Neoplasm - genetics / Epigenesis, Genetic / Epigenetic inheritance / Epigenetic modification / Epigenetics / Evolution & development / Gene Expression Regulation, Neoplastic / Health aspects / Homeostasis / Humans / Immunotherapy / Kinases / Metabolic pathways / Metabolism / Metastasis / MicroRNAs / Mitochondria / Mitochondria - genetics / Mitochondria - metabolism / Molecular modelling / Mutation / Neoplasms - drug therapy / Neoplasms - genetics / Neoplasms - metabolism / Neoplasms - pathology / Non-coding RNA / Non-coding RNAs / Oncology / Physiological aspects / Proteins / Review / RNA, Untranslated - genetics / Stem cells / Toxicity / Tumor suppressor genes / Tumors