Title:Bcl11a and the Correlated Key Genes Ascribable to Globin Switching: An
In-silico Study
Volume: 22
Issue: 2
Author(s): Fatemeh Movahedi Motlagh, Hamid Reza Soleimanpour-Lichaei, Ali Emami, Sepideh Kadkhoda, Mehdi Shamsara, Azam Rasti and Mohammad Hossein Modarressi*
Affiliation:
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Keywords:
In-silico study, systems biology, differentially expressed mRNAs, miRNAs, fetal and adult erythroblasts, globin switching.
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 posttranscriptional
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, hsamiR-
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.
