Circular RNAs in Breast Cancer Immunometabolism: Mechanisms of Immune Regulation and Metabolic Reprogramming.

Authors

Hailiang Jing, Jianing Jian, Chen Xing, Hong Luo

Published in

Critical reviews in oncology/hematology. Pages 105645. Oct 09, 2026. Epub Oct 09, 2026.

Abstract

Metabolic reprogramming and immune dysfunction are increasingly recognized as interconnected hallmarks of breast cancer progression, collectively shaping tumor evolution, immune evasion, and therapeutic response. Emerging evidence identifies circular RNAs (circRNAs), a highly stable class of endogenous non-coding RNAs generated through back-splicing, as pivotal regulators of the immunometabolic crosstalk within the breast cancer tumor microenvironment (TME). Through diverse mechanisms, including microRNA sequestration, interactions with RNA-binding proteins, and modulation of transcriptional and signaling networks, circRNAs coordinate metabolic pathways such as glycolysis, lipid metabolism, glutamine utilization, and mitochondrial function while simultaneously regulating immune cell differentiation, cytokine signaling, and immune checkpoint pathways. These coordinated metabolic and immunological alterations promote the establishment of an immunosuppressive TME characterized by the accumulation of regulatory T cells, myeloid-derived suppressor cells, tumor-associated M2 macrophages, and dysfunctional cytotoxic lymphocytes, thereby facilitating tumor progression, immune escape, and resistance to both conventional therapies and immunotherapy. In this narrative review, we provide a structured synthesis of current evidence on how circRNAs participate in the intersection of metabolic reprogramming and immune regulation in breast cancer. Particular emphasis is placed on mechanistically supported interactions linking circRNAs with glycolysis, mitochondrial metabolism, lipid and glutamine metabolism, immune-cell function, and immune-checkpoint regulation, while evidence derived from non-breast-cancer models is explicitly distinguished from breast-cancer-specific findings. Finally, we explore the emerging clinical applications of circRNAs as diagnostic and prognostic biomarkers and evaluate their potential as therapeutic targets for immunometabolic intervention, emphasizing their promise for improving immunotherapeutic efficacy and advancing precision medicine in breast cancer.

PMID:
42854996
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.

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