Identification of novel drug targets for diamond-blackfan anemia based on RPS19 gene mutation using protein-protein interaction network

Abbas Khan,Muhammad Junaid,Chang Liu,William C S Cho,Aman Chandra Kaushik,Dong-Qing Wei,Arif Ali

doi:10.1186/s12918-018-0563-0

Abbas Khan, Muhammad Junaid + Show 5 more

Open Access

https://doi.org/10.1186/s12918-018-0563-0

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Abstract

BackgroundDiamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy. In order to explore the molecular mechanisms of wild and mutated samples from DBA patients were exposed to bioinformatics investigation. Biological network of differentially expressed genes was constructed. This study aimed to identify novel therapeutic signatures in DBA and uncovered their mechanisms. The gene expression dataset of GSE14335 was used, which consists of 6 normal and 4 diseased cases. The gene ontology (GO), as well as Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and then protein–protein interaction (PPI) network of the identified differentially expressed genes (DEGs) was constructed by Cytoscape software.ResultsA total of 607 DEGs were identified in DBA, including 433 upregulated genes and 174 downregulated genes. GO analysis results showed that upregulated DEGs were significantly enriched in biological processes, negative regulation of transcription from RNA polymerase II promoter, chemotaxis, inflammatory response, immune response, positive regulation of cell proliferation, negative regulation of cell proliferation, response to mechanical stimulus, positive regulation of cell migration, response to lipopolysaccharide, and defence response. KEGG pathway analysis revealed the TNF signalling pathway, Osteoclast differentiation, Chemokine signalling pathway, Cytokine -cytokine receptor interaction, Rheumatoid arthritis, Biosynthesis of amino acids, Biosynthesis of antibiotics and Glycine, serine and threonine metabolism. The top 10 hub genes, AKT1, IL6, NFKB1, STAT3, STAT1, RAC1, EGR1, IL8, RELA, RAC3, mTOR and CCR2 were identified from the PPI network and sub-networks.ConclusionThe present study flagged that the identified DEGs and hub genes enrich our understanding of the molecular mechanisms underlying the development of DBA, and might shine some lights on identifying molecular targets and diagnostic biomarkers for DBA.

Highlights

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy
DiamondBlackfan anemia (DBA) is categorized as a rare genetic diseases characterized by cancer predisposition, bone marrow failure, pro-apoptotic haematopoiesis and congenital anomalies
Chiocchetti et al reported that RPS19 interact with PIM-1 oncoprotein in DBA

Summary

Introduction

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy. Diamond-Blackfan anemia (DBA) is a rare disease mostly affecting child during infancy This disease is characterized by defect in red blood cells which result in the reduction or absence of erythroid precursors in bone marrow. The cephalic area is affected in most of the cases but other parts such as heart, limb and tract were reported This disease is a complicated disorder, its evolution remains erratic [1, 2]. DiamondBlackfan anemia (DBA) is categorized as a rare genetic diseases characterized by cancer predisposition, bone marrow failure, pro-apoptotic haematopoiesis and congenital anomalies. There is a case control study reported that patient with DBA has reduced RPS gene expression and so ribosomal synthesis defect is the underlying cause of DBA [11]. It is necessary to find a feasible and cost-effective way of treatment

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