MicroRNA Modulation in Breast Cancer Drug Resistance

Breast cancer drug resistance remains a major impediment to improved patient outcomes, driven in part by microRNAs (miRNAs) that modulate gene networks governing cell survival, apoptosis and drug efflux. Dysregulated miRNA expression can suppress tumour-suppressor genes or enhance oncogenic pathways, thereby diminishing the efficacy of chemotherapy, endocrine therapy and targeted agents. Key mechanisms include direct repression of pro-apoptotic factors, activation of survival signalling cascades such as PI3K/Akt, alteration of hormone-receptor signalling and promotion of epithelial-to-mesenchymal transition. MiRNA profiles not only serve as biomarkers for emerging resistance but also present therapeutic targets: antagomiRs and miRNA mimics offer complementary strategies to restore chemosensitivity. Integrating miRNA modulation into clinical protocols holds promise for overcoming resistance across diverse breast cancer subtypes and improving long-term control of the disease.

Research from Nature Portfolio

A study has characterised microRNA-130b as a critical mediator of multidrug resistance in breast cancer. Elevated miR-130b levels were observed in chemoresistant cell lines and patient tumours, correlating inversely with the tumour suppressor PTEN. Overexpression of miR-130b enhanced proliferation and survival in the presence of anthracyclines and taxanes by sustaining PI3K/Akt signalling. Conversely, miR-130b inhibition restored PTEN expression, reduced Akt phosphorylation and sensitised resistant cells to chemotherapy both in vitro and in xenograft models. This work identifies the miR-130b–PTEN axis as a promising target for adjunct therapies aimed at reversing acquired chemoresistance.

MicroRNA Modulation in Breast Cancer Drug Resistance publication trend

The graph below shows the total number of articles in microrna modulation in breast cancer drug resistance across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): Small non-coding RNA molecules (19–25 nucleotides) that regulate gene expression post-transcriptionally by base-pairing with target mRNAs.

AntagomiR: Chemically modified oligonucleotides designed to bind and inhibit specific endogenous miRNAs, reversing their regulatory effects.

P-glycoprotein: ATP-dependent membrane pump that exports chemotherapeutic agents from cancer cells, contributing to multidrug resistance.

Neoadjuvant therapy: Treatment given before the primary intervention (usually surgery) to reduce tumour burden and assess in vivo drug sensitivity.

Phosphatase and tensin homolog (PTEN): Tumour-suppressor lipid phosphatase that antagonises PI3K/Akt signalling, regulating cell growth and survival.

PI3K/Akt signalling pathway: Intracellular cascade activated by growth factors; promotes proliferation and inhibits apoptosis, frequently hyperactivated in resistant tumours.

References

1. Targeting miR-21 to Overcome P-glycoprotein Drug Efflux in Doxorubicin-Resistant 4T1 Breast Cancer. Biomaterials Research (2024).
2. Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA. International Journal of Molecular Sciences (2023).
3. Dysregulation of MiR-21, MiR-221 and MiR-451 During Neoadjuvant Treatment of Breast Cancer: A Prospective Study. Biomolecules (2024).
4. MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway. Scientific Reports (2017).