Extracellular vehicles (EVs) have been broadly studied in hematopoiesis for nearly a decade. These vesicles carry various functional biomolecules including RNA families such as microRNAs (miRNA). These EVs-derived microRNAs have numerous roles in cell-cell interactions and are considered promising biomarkers for disease severity. However, this field lacks clinical studies of thrombopoiesis. In this study, EV specific miRNAs were isolated from the plasma of thrombocytopenic malaria patients.
Methods: EVs were purified from the plasma of thrombocytopenic malaria patients. EV-derived miRNAs were then prepared and abundance of miR-146, miR-28, miR-135 and miR‑203 were assessed in these samples. Quantitative polymerase chain reaction was performed, and relative expression of each miRNA was calculated using hsa-miR-451a as endogenous control. Then, the targets of up-regulated miRNAs and relevant pathways were predicted by using bioinformatics. Receiver Operating Characteristic with Area Under the Curve (AUC) was then calculated to assess their diagnostic potential.
Results: The relative expression of miR-146 and miR‑203 was higher in thrombocytopenic malaria patients compared to uninfected individuals. Bioinformatic analysis revealed that these miRNAs might regulate genes involved in the hematopoiesis pathway and the transforming growth factor pathways. All up-regulated miRNAs could potentially be used as disease biomarkers as determined by AUC; however, the sensitivity and specificity require further investigation.
Conclusion: An upregulation of miR-146 and miR‑203 was observed in in thrombocytopenic malaria patients. These findings will require further validation in larger cohort groups of malaria patients to fully understand the contribution of these EVs miRNAs to thrombopoiesis and biology.