The role of circRNAs in N6-methyladenosine(m6A), cell death and clinical applications in human breast cancer

Sep 23, 2026

Breast cancer remains the most frequently diagnosed malignancy among women worldwide, yet advances in diagnosis and treatment have not translated into earlier detection or markedly better patient outcomes. Key barriers include late-stage presentation, metastasis, recurrence, metabolic reprogramming, and drug resistance, creating an urgent need for reliable predictive indicators and diagnostic markers. Circular RNAs (circRNAs) are non-coding RNAs present across tissues and cells and act as biomarkers for diseases in nervous, cardiovascular, and immune systems. They promote tumorigenesis by regulating proliferation, metastasis, angiogenesis, and the tumor microenvironment. This narrative review consolidates current knowledge on circRNAs in breast cancer, covering biogenesis, characteristics, methylation, tumor cell death, and the translational potential for patients.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Introduction

CircRNAs biogenesis and molecular features

The role of circRNAs in N6-methyladenosine(m6A), cell death and clinical applications in human breast cancer Science Progress Vol. 109(2): 1–18 © The Author(s) 2026 Article reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions) [DOI: 10.1177/00368504261436956](DOI: 10.1177/00368504261436956) [journals.sagepub.com/home/sci](journals.sagepub.com/home/sci) Shuting Chen1,2,*, Jiahui Mao3,*, Xiufen Zhuang4, Yifan Jiang5, Yichen Zou5, Min Xiang5, and Yang Shu5 Abstract Breast cancer (BC) is widely recognized as the most frequently diagnosed neoplasm among women worldwide. Despite significant advances, improved diagnosis and treatment of breast cancer have failed to translate into earlier detection or markedly better outcomes for patients, due to challenges including late-stage presentation, metastasis, recurrence, metabolic reprogramming, and drug resistance. Identifying reliable predictive indicators for early intervention and diagnostic markers remains a priority in breast cancer research, as this is crucial for improving patient prognosis. Circular RNAs (circRNAs), a class of non-coding RNAs (ncRNAs) abundant in various tissues and human cells, are established biomarkers for diagnosing and monitoring diseases such as those affecting the nervous, cardiovascular, and immune systems. CircRNAs contribute to tumorigenesis through the regulation of proliferation, metastasis, angiogenesis, and the tumor microenvironment. A growing body of evidence has established circRNAs as key regulators in breast cancer, elucidating their specific roles in driving tumor development and progression. Nevertheless, a more comprehensive understanding of the functional roles and molecular mechanisms of circRNAs in BC is essential and requires further research. This narrative review synthesizes the current knowledge on circRNAs encompassing their biogenesis, characteristics, methylation, tumor cell death, and selectively analyzes the translational potential of circRNAs in BC patients. Keywords autophagy, metabolism, methylation, RNA binding protein, immunotherapy Received: 13 September 2025; Revised: 6 March 2026; Accepted: 12 March 2026 1Department of Pharmacy, The Central Hospital of Yongzhou, China 2Department of Pharmacy, Yongzhou Hospital Affiliated to University of South China, China 3Department of Central Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China 4Department of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China 5Department of Clinical Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China *These authors contributed equally to this paper. Corresponding authors: Min Xiang, Department of Clinical Laboratory, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, Jiangsu, China. Email: [zlxiang43@163.com](zlxiang43@163.com) Yang Shu, Department of Clinical Laboratory, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, Jiangsu, China. Email: [ushyang@ujs.edu.com](ushyang@ujs.edu.com) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ([https://us.sagepub.com/en-us/nam/open-access-at-sage](https://us.sagepub.com/en-us/nam/open-access-at-sage)). Introduction Breast Cancer (BC) remains one of the most frequently diagnosed malignant tumors and a leading cause of cancer-related morbidity and mortality among women worldwide.1–3 In the European Union (EU), the second leading cause of cancer death among females is breast cancer with age-standardised rates (ASRs

FAQs

Why are new diagnostic markers and predictive indicators needed in breast cancer research?

Improved diagnosis and treatment have not enabled earlier detection or substantially better outcomes due to late-stage presentation, metastasis, recurrence, metabolic reprogramming, and drug resistance.

What are circRNAs and why are they considered stable biomarker candidates?

CircRNAs are non-coding RNAs with a covalently closed circular structure produced via back-splicing; their circular conformation gives inherent stability and resistance to RNase R.

How do circRNAs contribute to breast cancer development and progression?

They contribute to tumorigenesis by regulating proliferation, metastasis, angiogenesis, and shaping the tumor microenvironment through specific molecular mechanisms.

Sep 23, 2026

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