MicroRNA Mechanisms in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype defined by the absence of oestrogen, progesterone and HER2 receptors, rendering it unresponsive to conventional targeted therapies. MicroRNAs (miRNAs) are small non-coding RNAs of 19–25 nucleotides that fine-tune gene expression post-transcriptionally by binding to complementary sequences in messenger RNAs. In TNBC, dysregulated miRNAs act as oncogenes or tumour suppressors to control cell proliferation, apoptosis, epithelial-to-mesenchymal transition (EMT), stem-cell characteristics and metastasis. Key miRNAs such as miR-21 and miR-155 are frequently upregulated and promote invasion, whereas members of the miR-200 family are often downregulated, releasing repression of EMT-related transcription factors. Aberrant miRNA expression also modulates the tumour microenvironment by influencing immune signalling and inflammasome activation, and contributes to chemoresistance by targeting genes involved in cell-cycle regulation and drug metabolism. Profiling of circulating miRNAs in serum or plasma offers a minimally invasive route to diagnosis, prognosis and treatment monitoring, with emerging signatures achieving high sensitivity and specificity. Advances in delivery systems for miRNA mimics or antagonists hold promise for future therapeutic interventions in TNBC.

Research from Nature Portfolio

Recent studies have demonstrated the potential of a three-miRNA serum signature for early diagnosis of TNBC. Elevated levels of miR-155 and miR-21, combined with reduced expression of miR-205, were validated across multiple patient cohorts, achieving diagnostic accuracy above 94 per cent. Quantitative analyses showed that this panel distinguishes TNBC patients from healthy controls with an area under the receiver operating characteristic curve consistently exceeding 0.95. Such robust performance underlines the promise of circulating miRNAs as independent, non-invasive biomarkers for patient stratification and may guide personalised management.

MicroRNA Mechanisms in Triple-Negative Breast Cancer publication trend

The graph below shows the total number of articles in microrna mechanisms in triple-negative breast cancer across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): A small non-coding RNA molecule that binds to complementary messenger RNA sequences to inhibit translation or promote degradation.

Triple-negative breast cancer (TNBC): A subtype of breast cancer lacking oestrogen receptor, progesterone receptor and HER2 expression, associated with poor prognosis.

Epithelial-to-mesenchymal transition (EMT): A biological programme in which epithelial cells acquire mesenchymal characteristics, enhancing motility and invasiveness.

Inflammasome: A multiprotein complex within immune cells that activates inflammatory responses through caspase-1 and cytokine maturation.

Pyroptosis: A form of programmed cell death characterised by inflammatory cytokine release and membrane pore formation.

References

1. Regulation of Inflammasome by microRNAs in Triple-Negative Breast Cancer: New Opportunities for Therapy. International Journal of Molecular Sciences (2023).
2. Impact of three miRNA signature as potential diagnostic marker for triple negative breast cancer patients. Scientific Reports (2023).
3. New progress in the role of microRNAs in the diagnosis and prognosis of triple negative breast cancer. Frontiers in Molecular Biosciences (2023).
4. MiRNA and LncRNA as Potential Biomarkers in Triple-Negative Breast Cancer: A Review. Frontiers in Oncology (2020).