Molecular pathways and gene networks in fetal hemoglobin as a novel protein target for beta-thalassemia

Background: Beta thalassemia is a condition in which the body cannot produce the beta subunit of hemoglobin due to harmful mutations in the globin gene that cause inadequate development of adult hemoglobin (HbA). In beta-thalassemic individuals, fetal hemoglobin (HbF), consisting of two and two subunits, is a potential replacement for HbA with significant therapeutic importance. HbF increase is a powerful and essential therapeutic tool to overcome the problem of beta-thalassemia. Materials and Methods: The GEO2R statistical tool and the GSE96060 dataset from the gene expression omnibus database were used to determine the differentially expressed genes (DEGs). The search tool for the retrieval of interacting genes program was used to reveal connections between these DEGs in samples, followed by applying the molecular complex detection algorithm to identify clusters of genes within these interaction networks. Using ClueGo and CluePedia, the discovered DEGs were subjected to functional annotation, including gene ontology (GO) and enriched molecular pathway analysis. Results: We searched the top 200 DEGs that met the criteria for significance (P-value 0.05; fold two change >1 or 1). Myeloid cell differentiation, erythrocyte differentiation, cellular detoxification, and heme binding are only a few examples of the biological processes and molecular pathways the GO analysis of DEGs identified as having significant alterations. The link between the DEGs in heme biosynthesis and transcriptional dysregulation in cancer was discovered by studying enriched Kyoto encyclopedia of genes and genomes pathways. To find possible targets for beta thalassemia treatments, we looked for the genes Krüppel-like factors 1 (KLF1) and mouse double minute 2 (MDM2). By activating both beta-globin and HbF gamma-globin genes, KLF1 encourages HbF repression, which is regulated by changing myeloblastosis expression. Conclusion: This study shows that the genes KLF1 and MDM2 are related to dysregulated molecular pathways, contribute to the development of beta thalassemia, and may be exploited as a platform for the induction of fetal hemoglobin in the development of therapeutics.