Affiliation:
1. Instituto de Ciencias Biomédicas (ICBM), Facultad de Ciencias Médicas, Universidad Católica de Cuyo, Av. José Ignacio de la Roza 1516, Rivadavia, 5400, San Juan, Argentina.
2. CONICET – Universidad de Buenos Aires. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Laboratorio de Inflamación y Cáncer. Buenos Aires, Argentina
3. Department of Hematology and Medical Oncology, Morales Meseguer University Hospital, Centro Regional de Hemodonación, Universidad de Murcia, IMIB, C/Ronda de Garay S/N, 30003 Murcia, Spain.
Abstract
Abstract
Despite advancements in B-cell acute lymphoblastic leukemia (B-ALL) therapy, a significant number of patients still experience treatment resistance, leading to relapse and poor prognosis. Recent studies have revealed the importance of non-genetic mechanisms in mediating resistance to cancer therapies. MicroRNAs (miRNAs) have emerged among non-genetic mechanisms as crucial regulators of tumor development, progression, and resistance to anticancer therapies. In particular, miR-34a has been implicated in cell invasion, migration, apoptosis, and abnormal response to chemotherapy in various tissues. However, the role of miR-34a-5p in B-ALL cells remains unexplored. Our results discovered that miR-34a-5p was downregulated in B-ALL cells, while its target SIRT1 was upregulated. Although the restoration of miR-34a-5p levels did not affect SIRT1 levels in B-ALL cells, restoring miR-34a-5p sensitized the cells to doxorubicin treatment. Additionally, to explain these results, we performed an extensive bioinformatic analysis in human B-ALL samples downloaded from online repositories to study miR-34a-5p as a potential biomarker for predicting response to B-ALL treatment. Notably, miR-34a-5p was observed to be downregulated in B-ALL cells from relapsed patients. We also identified four genes targeted by miR-34a-5p in these patient cells, which had not been previously associated with B-ALL. Finally, miR-34a-5p, PRR11, and SURF4 were identified as independent predictive markers for increased risk of death in B-ALL patients. Overall, these findings shed light on the significance of miR-34a-5p in B-ALL cells, and suggest that the combination of miR-34a-5p, PRR11, and SURF4 hold promise as potential markers for estimating the survival outcomes of B-ALL patients.
Publisher
Research Square Platform LLC