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ADAR1介导的乳腺癌RNA编辑:分子机制与治疗意义

ADAR1-mediated RNA editing in breast cancer: molecular mechanisms and therapeutic implications.

作者信息

Chen Si-Yu, Chen Si-Ying, Yang Shu, Li Yi, Yang Sheng-Yong

机构信息

Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.

出版信息

Med Oncol. 2025 Aug 9;42(9):421. doi: 10.1007/s12032-025-02979-9.

Abstract

Breast cancer (BC) continues to be among the most widespread and clinically demanding cancers globally, resulting in significant illness and death, even with progress in early detection and treatment approaches. Traditional therapeutic modalities, including surgery, chemotherapy, and targeted therapies, often fail in the face of drug resistance, metastasis, and the invasion. Consequently, a pressing demand exists for new biomarkers and treatment approaches to enhance clinical results. A recent area of focus in cancer research is RNA editing, particularly the role of Adenosine deaminase acting on RNA1 (ADAR1) which operates as an RNA editing enzyme that catalyzes adenosine-to-inosine conversion within double-stranded RNA substrates. This process affects gene expression and various cellular functions including RNA stability, splicing, and translation. Recent studies have highlighted the important function of ADAR1 editing in several types of cancer, including breast cancer, by regulating key pathways that are critical to tumor development, proliferation, and therapeutic resistance. This review aims to inspire further research into ADAR1-mediated mechanisms, offering new perspectives to overcome therapeutic resistance and improve clinical outcomes. This review systematically examines the multifaceted roles of ADAR1 in breast cancer progression, with a focus on its upstream regulators and downstream effects on critical pathways. Our analysis not only consolidates current understanding of ADAR1's regulatory networks, but also pointed out the current problems with ADAR1 in breast cancer research. What's more, we also proposed innovative strategies such as ADAR1 inhibitors to advance precision medicine in breast cancer.

摘要

乳腺癌(BC)仍然是全球范围内最普遍且临床需求高的癌症之一,即便在早期检测和治疗方法上取得了进展,仍导致大量疾病和死亡。传统治疗方式,包括手术、化疗和靶向治疗,在面对耐药性、转移和侵袭时常常失效。因此,迫切需要新的生物标志物和治疗方法来提高临床疗效。癌症研究中一个近期的关注领域是RNA编辑,特别是作用于RNA1的腺苷脱氨酶(ADAR1)的作用,它作为一种RNA编辑酶,催化双链RNA底物内腺苷向肌苷的转化。这个过程影响基因表达和各种细胞功能,包括RNA稳定性、剪接和翻译。最近的研究强调了ADAR1编辑在包括乳腺癌在内的几种癌症中的重要功能,通过调节对肿瘤发展、增殖和治疗耐药性至关重要的关键途径。本综述旨在激发对ADAR1介导机制的进一步研究,为克服治疗耐药性和改善临床结果提供新的视角。本综述系统地研究了ADAR1在乳腺癌进展中的多方面作用,重点关注其上游调节因子以及对关键途径的下游影响。我们的分析不仅巩固了目前对ADAR1调控网络的理解,还指出了乳腺癌研究中ADAR1目前存在的问题。此外,我们还提出了诸如ADAR1抑制剂等创新策略,以推进乳腺癌的精准医学。

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