Exploring the time-dependent regulatory potential of microRNAs in breast cancer cells treated with proteasome inhibitors
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Katerina Katsaraki [1] ; Christos K. Kontos [1] ; Gerasimos Ardavanis-Loukeris [2] ; Alexandros A. Tzovaras [2] ; Diamantis C. Sideris [1] ; Andreas Scorilas [1]
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[1] National and Kapodistrian University of Athens
National and Kapodistrian University of Athens
Dimos Athens, Grecia
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[2] First Department of Medical Oncology, “Saint Savvas” General Anticancer Hospital of Athens, Athens, Greece
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- Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 26, Nº. 5, 2024, págs. 1259-1267
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
Purpose Breast cancer (BrCa) is a predominant type of cancer with a disparate molecular nature. MicroRNAs (miRNAs) have emerged as promising key players in the regulation of pathological processes in BrCa. Proteasome inhibitors (PIs) emerged as promising anticancer agents for several human malignancies, including BrCa, inhibiting the function of the proteasome. Aiming to shed light on the miRNA regulatory effect in BrCa after treatment with PIs, we used two PIs, namely bortezomib and carfilzomib.
Materials and methods Four BrCa cell lines of distinct molecular subtypes were treated with these PIs. Cell viability and IC50 concentrations were determined. Total RNA was extracted, polyadenylated, and reversely transcribed. Next, the levels of specific miRNAs with a significant role in BrCa were determined using relative quantification, and their regulatory effect was assessed.
Results High heterogeneity was discovered in the levels of miRNAs in the four cell lines, after treatment. The miRNA levels fluctuate with distinct patterns, in 24, 48, or 72 hours. Interestingly, miR-1-3p, miR-421-3p, and miR-765-3p appear as key molecules, as they were found deregulated, in almost all combinations of cell lines and PIs. In the SK-BR-3 cell line, the majority of the miRNAs were significantly downregulated in treated compared to untreated cells, with miR-21-5p being the only one upregulated. Finally, various significant biological processes, molecular functions, and pathways were predicted to be affected.
Conclusions The diversity of pathways predicted to be affected by the diversity in miRNA expression after treatment with PIs paves the way for the recognition of new regulatory axes in BrCa.
