Navigating the nexus: Dysregulation of non-coding RNAs in breast cancer under therapeutic interventions - Mechanisms and clinical implications

Abstract

Non-coding RNAs (ncRNAs)-including micro RNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)-are key regulators of gene expression in the biological processes of breast cancer (BC) development. The dysregulation of these ncRNAs also contributes majorly to the initiation, progression, and treatment resistance of BC. This review summarizes the current understanding of how systemic therapeutic strategies (e.g. chemotherapy, endocrine therapy, targeted therapy, radiotherapy, and immunotherapy) can induce ncRNA changes which subsequently alter treatment responses. The underlying dysregulation of ncRNAs in BC occur through genetic events, epigenetic alterations, and complex transcriptional and post-transcriptional regulatory events, including competing endogenous RNA (ceRNA) networks. Some ncRNAs are important mediators of drug resistance (e.g. miR-21 in chemoresistance, HOTAIR in endocrine resistance, and ncRNAs regulated by ALKBH5 in HER2-targeted therapy resistance), modulating biological pathways such as apoptosis, DNA repair, and drug metabolism. The sensitivity of ncRNAs in biofluids make them appealing candidates for non-invasive biomarkers for diagnosis, prognosis, and real-time monitoring of response to treatment interventions. Despite the clear potential for ncRNAs to serve as therapeutic targets and as biomarkers in clinical management of BC, additional work is required to generate optimal delivery methods, achieve specificity, and standardize detection methods. Future studies, encompassing 'multi-omics' strategies in BC research together with enhanced computational tools, will also be warranted to fully establish ncRNA discoveries into personalized BC care, and improved treatment outcomes for patient management through precision nanomedicine and liquid biopsy platforms.

Keywords: Breast cancer; Chemotherapy; Epigenetics; ncRNA.