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Clinical Identification of Dysregulated Circulating microRNAs and Their Implication in Drug Response in Triple

Amal Qattan1,2, Taher Al-Tweigeri3, Wafa Alkhayal4

  • 1Breast Cancer Research, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.

Genes
|April 30, 2021
PubMed

Insights

Circulating microRNAs (miRNAs) are key regulators of drug resistance in triple-negative breast cancer (TNBC). Identifying these miRNAs offers potential for personalized medicine and improved treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biomarkers

Background:

  • Therapy resistance significantly contributes to mortality in breast cancer, especially triple-negative breast cancer (TNBC).
  • MicroRNAs (miRNAs) are recognized as crucial regulators of gene networks involved in drug resistance.
  • Circulating miRNAs show promise as non-invasive biomarkers for TNBC diagnosis, prognosis, and predicting drug response.

Purpose of the Study:

  • To elucidate drug resistance pathways and clinical outcomes linked to circulating miRNAs in TNBC patients using systems biology and meta-analysis.
  • To identify specific circulating miRNAs and their target genes/pathways implicated in TNBC drug resistance.
  • To explore the potential of circulating miRNAs as predictive biomarkers for personalized medicine in TNBC.

Main Methods:

  • MiRNA expression analysis to identify differentially regulated circulating miRNAs in TNBC.
  • Integrated pathway analysis, gene ontology, and pharmacogenomic network analysis to map miRNA-target interactions.
  • Meta-analysis to correlate miRNA expression with overall survival outcomes in TNBC patients.

Main Results:

  • Six circulating miRNAs (miR-19a/b-3p, miR-25-3p, miR-22-3p, miR-210-3p, miR-93-5p, miR-199a-3p) were identified as significantly differentially expressed in TNBC.
  • These miRNAs regulate key pathways involved in drug resistance, including PI3K/Akt/mTOR, HIF-1, TNF, FoxO, Wnt, JAK/STAT, PD-1/PD-L1, and EGFR tyrosine kinase inhibitor resistance.
  • Upregulation of miR-93, miR-210, miR-19a, and miR-19b was associated with poorer overall survival in TNBC patients.

Conclusions:

  • Circulating miRNAs play a significant role in regulating drug resistance mechanisms in TNBC.
  • Specific circulating miRNAs can serve as potential biomarkers for predicting drug response and resistance.
  • Integrated multi-dimensional data analysis is effective in uncovering miRNA-driven drug resistance mechanisms for personalized TNBC treatment strategies.
Keywords:
chemoresistancecirculating miRNAtheranostic markerstriple-negative breast cancer

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