Construction and Analysis of miRNA-mRNA Network Related to Erythroid Differentiation in Chronic Myeloid Leukemia

Wang Jingyan; Yang Yu; Zhang Tao

doi:10.3969/j.issn.1004-5775.2025.05.001

Abstract：Objective:To identify miRNA and mRNA that play a key role in erythroid differentiation of chronic myeloid leukemia(CML),and to reveal the network regulatory relationship between them and their effects on signaling pathways.Methods:With GEO database,the miRNAs and mRNAs with significantly altered expression after erythroid differentiation of CML were identified.With TarBase v.8 of the DIANA tools analysis platform and Cytoscape software,a miRNA-mRNA regulatory network was constructed.Further,the key hub miRNAs were identified.The KEGG signaling pathway enrichment analysis was performed on miRNAs and mRNAs with mirPath v.3 tool from the DIANA tools analysis platform and the Metascape analysis platform,respectively.Finally,the impact of erythroid differentiation on the expression of hub miRNAs in CML cells was validated by Quantitative Real-Time PCR.Results:A total of 4 281 mRNAs and 475 miRNAs with significantly different expression were screened,among which the genes with the most significant differences include ATP2A3,CXCL8,hsa-miR-219a-5p and hsa-miR-154-5p,etc.miRNA-mRNA network analysis revealed that 4 miRNAs,including hsa-miR-520c-3p,serve as network hubs for significantly reduced expression,while eleven miRNAs,including hsa-miR-128-3p,serve as network hubs for significantly increased expression.Signal pathway enrichment analysis found that the differentially expressed miRNAs and mRNAs were primarily enriched in pathways,such as PI3K-Akt signaling,etc.The results of in vitro experiments showed that in K562 cells treated with hemin,the relative expression of hsa-miR-520c-3p was significantly decreased,while the relative expression of hsa-miR-128-3p was significantly increased.Conclusion:The regulatory role of miRNA and mRNA in CML erythroid differentiation is comprehensively discussed by constructing miRNA-mRNA network,and the key miRNA and signaling pathways is revealed,which provides a new perspective for understanding the regulatory mechanism of CML erythroid differentiation and a potential target for CML treatment.