MiR-15a-5p Confers Chemoresistance in Acute Myeloid Leukemia by Inhibiting Autophagy Induced by Daunorubicin.

Bollaert, Emeline;Claus, Melissa;Vandewalle, Virginie;Lenglez, Sandrine;Havelange, Violaine;et.al.
(2021) International journal of molecular sciences — Vol. 22, n° 10, p. 5153 (2021)

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Abstract
Anthracyclines remain a cornerstone of induction chemotherapy for acute myeloid leukemia (AML). Refractory or relapsed disease due to chemotherapy resistance is a major obstacle in AML management. MicroRNAs (miRNAs) have been observed to be involved in chemoresistance. We previously observed that was overexpressed in a subgroup of chemoresistant cytogenetically normal AML patients compared with chemosensitive patients treated with daunorubicin and cytarabine. overexpression in AML cells reduced apoptosis induced by both drugs in vitro. This study aimed to elucidate the mechanisms by which contributes to daunorubicin resistance. We showed that daunorubicin induced autophagy in myeloid cell lines. The inhibition of autophagy reduced cell sensitivity to daunorubicin. The overexpression of decreased daunorubicin-induced autophagy. Conversely, the downregulation of increased daunorubicin-induced autophagy. We found that targeted four genes involved in autophagy, namely and . Daunorubicin increased the expression of these four genes, and counteracted this regulation. Inhibition experiments with the four target genes showed the functional effect of on autophagy. In summary, our results indicated that induces chemoresistance in AML cells through the abrogation of daunorubicin-induced autophagy, suggesting that could be a promising therapeutic target for chemoresistant AML patients.
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Bollaert, E., Claus, M., Vandewalle, V., Lenglez, S., Essaghir, A., Demoulin, J. B., & Havelange, V. (2021). MiR-15a-5p Confers Chemoresistance in Acute Myeloid Leukemia by Inhibiting Autophagy Induced by Daunorubicin. International journal of molecular sciences, 22(10), 5153. https://doi.org/10.3390/ijms22105153 (Original work published 2021)