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Bcl11a and the Correlated Key Genes Ascribable to Globin Switching: An In-Silico Study Publisher Pubmed



Motlagh FM1 ; Soleimanpourlichaei HR2 ; Emami A3 ; Kadkhoda S1 ; Shamsara M4 ; Rasti A1 ; Modarressi MH1
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Stem Cells and Regenerative Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
  3. 3. Department of Animal Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran
  4. 4. Animal Biotechnology Group, Department of Agricultural Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

Source: Cardiovascular and Hematological Disorders - Drug Targets Published:2022


Abstract

Background: Reactivation of HbF is a potential strategy to ameliorate symptoms of hemoglobinopathies such as sickle cell disease and b-thalassemia. After birth, there is a switch from fetal to adult hemoglobin, for which the molecular mechanisms and key regulators await further understanding in order to develop effective methods for HbF reactivation. Bcl11a, one of the major HbF reactivation regulators, demonstrates no significant changes at transcriptional levels in F erythroblasts compared to the non-HbF expressing cells. Therefore, it is possible that post-transcriptional regulation and epigenetic effects, for which the miRNAs play an important role, are the primary causes of the decreased Bcl11a protein level in adult erythroblasts. Objective: This paper aims to determine the differentially expressed mRNAs and miRNAs of erythroblasts in HSCs from the fetal liver and bone marrow. Methods: Raw high-throughput sequencing data (GSE110936, GSE90878) was downloaded from Gene Expression Omnibus (GEO) database. After RNAseq analysis, several data sets and tools were used to select key genes and examine selection validation. Results: We selected 42 DEmRNAs and nine DEmiRs, including hsa-let-7f-5p, hsa-miR-21-5p, hsa-miR-22-3p, hsa-miR-126-5p, hsa-miR-146b-5p, hsa-miR-181a-5p, hsa-miR-92a-3p, hsa-miR-25-3p and hsa-miR-191-5p. Furthermore, hub genes including hist1h2bl, al133243.2, trim58, abcc13, bpgm, and fam210b were identified in the coexpression network, as well as RPS27A in the PPI network. Functional analysis revealed that these DEmRNAs and DEmiRs might play a role in gene expression regulation at multiple levels. Gene set enrichment analysis, in particular, revealed a possible role for genes in the globin switching process. Conclusion: According to our findings, a number of the DEmRNAs and DEmiRs may play significant roles in globin switching regulation and thus have the potential to be applied for HbF reactivation. © 2022 Bentham Science Publishers.
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