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

• Main Authors: Chen, M. (Author), Huang, H. (Author), Pan, Y. (Author), Wang, H. (Author), Xu, L. (Author), Xu, S. (Author), Zhang, Y. (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: Article; B-cell lymphoma/leukemia 11A; beta thalassemia; beta-Thalassemia; case control study; Case-Control Studies; Child, Preschool; clinical article; controlled study; DNA synthesis; down regulation; female; Female; gene expression profiling; Gene Expression Profiling; gene expression regulation; Gene Expression Regulation; gene regulatory network; Gene Regulatory Networks; gene silencing; genetic transcription; genetics; human; human cell; human serum albumin; Humans; let7 microRNA; male; Male; mean corpuscular hemoglobin; mean corpuscular volume; microRNA; microRNA 106a 5p; microRNA 17 5p; microRNA 20a 5p; microRNA 221 3p; microRNA 329 3p; microRNA 433 3p; microRNA 4435; microRNA 4508; microRNA 483 3p; microRNA 495 3p; microRNA 543; microRNA 6501 5p; microRNA 6747 3p; microRNA 92b 5p; microRNA 93 5p; microRNA let 7a 3p; microRNA let 7f 1 3p; microRNA let 7g 5p; microRNA let 7i 5p; microRNA let7b 5p; microRNA sequencing; MicroRNAs; morphogenesis; pathology; pediatric β-thalassemia; phosphatidylinositol 3 kinase; platelet count; preschool child; prognosis; Prognosis; protein kinase B; RNA isolation; RNA sequence; transcription regulation; transforming growth factor beta; transforming growth factor beta receptor; unclassified drug; upregulation; γ-globin reactivation
• Online Access: View Fulltext in Publisher

 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. © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.