Revealing Key LncRNAs in Cytogenetically Normal Acute Myeloid Leukemia by Reconstruction of the LncRNA–miRNA–mRNA Network Based on the Competitive Endogenous RNA Theory

Abstract

Background Cytogenetically normal acute myeloid leukemia(CN-AML) is a heterogeneous disease with different prognosis.Researches on prognostic indicators and therapy targets of CN-AML are still ongoing.Instead of protein-coding genes,more and more researches were focused on the non-coding RNAs especially long non-coding RNAs(lncRNAs) which may play an important role in the development and prognosis of AML.Although a large number of lncRNAs had been found, our knowledge of their function and pathological significance is still in its infancy.The purpose of this research is to identify the key lncRNAs and explore their function in CN-AML by reconstructing the lncRNA–miRNA–mRNA network based on the competitive endogenous RNA(ceRNA) theory. Results We reconstructed a global triple network based on the ceRNA theory using the data from National Center for Biotechnology Information Gene Expression Omnibus and published literature. According to the topological algorithm,we identified the key lncRNAs which had both the higher node degrees and the higher number of lncRNA–miRNA and miRNA–mRNA pairs in the ceRNA network. Meanwhile, Gene Ontology (GO) and pathway analysis were performed using databases such as DAVID,KOBAS and Cytoscape plug-in ClueGO respectively.The lncRNA–miRNA–mRNA network was composed of 90 lncRNAs,33mRNAs,26 miRNAs and 259 edges in the lncRNA upregulated group,and 18 lncRNAs,11 mRNAs,6 miRNAs and 45 edges in the lncRNA downregulated group.The functional assay showed that 53 pathways and 108 GO terms were enriched. Three lncRNAs(XIST,GABPB1-AS1,TUG1)could possibly be selected as key lncRNAs wihch may play an important role in the development of CN-AML.Particularly,GABPB1-AS1 was highly expressed in CN-AML by both bioinformatics analysis and experimental verification in AML cell line(THP-1) by quantitative real-time polymerase chain reaction.In addition, GABPB1-AS1 was also negatively correlated with overall survival of AML patients. Conclusion The lncRNA–miRNA–mRNA network revealed key lncRNAs and their functions in CN-AML.Particularly,lncRNA GABPB1-AS1 was firstly proposed in AML.We believe that GABPB1-AS1 is expected to become a candidate diagnostic biomarker or potential therapeutic target.