The CircRNA/miRNA axis in breast cancer: From molecular mechanisms to clinical translation

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Breast cancer is a leading cause of mortality, necessitating novel therapeutic strategies.
• Dysregulated non-coding RNA expression, including circular RNAs (circRNAs), is implicated in cancer pathogenesis.
• Current targeted therapies for breast cancer have limited efficacy, highlighting the need for new drug targets.

Purpose of the Study:

• To introduce a "functional integration" framework for understanding circular RNA (circRNA) roles in disease.
• To explore circRNA functional modules as pharmacologically actionable targets for precision cancer interventions.
• To establish a foundation for circRNA-based liquid biopsy and targeted therapies.

Main Methods:

• Review of emerging evidence on circRNA functions beyond the ceRNA paradigm.
• Conceptualization of a "functional integration" model where circRNAs act as environmentally regulated "molecular toolkits".
• Identification of circRNA-encoded functional modules (e.g., protein interactions, peptide encoding) as potential therapeutic targets.

Main Results:

• CircRNAs can possess context-dependent functional modules activated by environmental signals to drive disease phenotypes.
• These modules represent novel targets for precision interventions, including small-molecule inhibitors, PROTACs, and immunotherapies.
• The framework supports the development of circRNA-based liquid biopsies and targeted therapeutic strategies.

Conclusions:

• Circular RNAs hold significant potential as targets for novel breast cancer therapies.
• The functional integration framework provides a new perspective for developing precision medicine approaches.
• Targeting specific circRNA functional modules can lead to more effective and tailored cancer treatments.