Abnormal regulation of microRNAs and related genes in pediatric β-thalassemia

Abstract

Background: MicroRNAs (miRNAs) participate in the reactivation of γ-globin expression in β-thalassemia. However, the miRNA transcriptional profiles of pediatric β-thalassemia remain unclear. Accordingly, in this study, we assessed miRNA expression in pediatric patients with β-thalassemia. Methods: Differentially expressed miRNAs in pediatric patients with β-thalassemia were determined using microRNA sequencing. Results: Hsa-miR-483-3p, hsa-let-7f-1-3p, hsa-let-7a-3p, hsa-miR-543, hsa-miR-433-3p, hsa-miR-4435, hsa-miR-329-3p, hsa-miR-92b-5p, hsa-miR-6747-3p and hsa-miR-495-3p were significantly upregulated, whereas hsa-miR-4508, hsa-miR-20a-5p, hsa-let-7b-5p, hsa-miR-93-5p, hsa-let-7i-5p, hsa-miR-6501-5p, hsa-miR-221-3p, hsa-let-7g-5p, hsa-miR-106a-5p, and hsa-miR-17-5p were significantly downregulated in pediatric patients with β-thalassemia. After integrating our data with a previously published dataset, we found that hsa-let-7b-5p and hsa-let-7i-5p expression levels were also lower in adolescent or adult patients with β-thalassemia. The predicted target genes of hsa-let-7b-5p and hsa-let-7i-5p were associated with the transforming growth factor β receptor, phosphatidylinositol 3-kinase/AKT, FoxO, Hippo, and mitogen-activated protein kinase signaling pathways. We also identified 12 target genes of hsa-let-7a-3p and hsa-let-7f-1-3p and 21 target genes of hsa-let-7a-3p and hsa-let-7f-1-3p, which were differentially expressed in patients with β-thalassemia. Finally, we found that hsa-miR-190-5p and hsa-miR-1278-5p may regulate hemoglobin switching by modulation of the B-cell lymphoma/leukemia 11A gene. Conclusion: The results of the study show that several microRNAs are dysregulated in pediatric β-thalassemia. Further, the results also indicate toward a critical role of let7 miRNAs in the pathogenesis of pediatric β-thalassemia, which needs to be investigated further.