The microRNA (miR) 155-5p plays a pivotal role in mediating programmed cell death ligand 1-mediated apoptosis of CD34+ cells in myelodysplastic syndromes (MDS), ultimately impacting bone marrow hematopoiesis, according to a study published in Mediterranean Journal of Hematology and Infectious Diseases.
The underlying molecular mechanism involves a signaling axis mediated by the Rac family small GTPase 1 (RAC1), the cAMP-response element binding protein (CREB), and miR-15b.
“To some extent, the findings may open up a new avenue for the development of molecule-based pharmaceutics for MDS. However, the relevant mechanism was only studied in cells, but not verified in animal experiments. Also, more rigorous experimental protocols should be designed to validate the role and mechanism of miR-155-5p in MDS,” the study’s authors concluded.
The results of the study showed that miR-155-5p was upregulated in the bone marrow of patients with MDS. Further experiments confirmed that miR-155-5p promotes apoptosis of CD34+ cells isolated from bone marrow.
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Moreover, the study demonstrated that miR-155-5p inhibits the transcriptional activity of miR-15b by suppressing RAC1, thereby disrupting the interaction between RAC1 and CREB, and inhibiting CREB activation. It also induced programmed cell death ligand 1 expression, an effect that was mitigated by upregulating RAC1, CREB, or miR-15b expression.
In addition, upregulation of RAC1, CREB, or miR-15b reduced the apoptosis enhancing effect of miR-155-5p in CD34+ cells.
Altogether, these findings provide valuable insights into the underlying mechanisms of MDS and may contribute to the development of targeted interventions.
The study involved the collection of bone marrow samples from patients with MDS to detect miR-155-5p. Isolated bone marrow CD34+ cells were transfected with lentiviral plasmids that interfere with miR-155-5p, and subsequent apoptosis analysis was conducted.
Cao M, Peng B, Xu W, et al. The mechanism of miR-155/miR-15b axis contributed to apoptosis of CD34+ cells
by upregulation of PD-L1 in myelodysplastic syndromes. Mediterr J Hematol Infect Dis. Published online June 29, 2023. doi:10.4084/MJHID.2023.040.