The characteristics of circRNA as competing endogenous RNA in pathogenesis of acute myeloid leukemia

Abstract

Background: As one of the novel molecules, circRNA has been identified closely involved in the pathogenesis of many diseases. However, the function of circRNA in acute myeloid leukemia (AML) still remains unknown.

Methods: In the current study, the RNA expression profiles were obtained from Gene Expression Omnibus (GEO) datasets. The differentially expressed RNAs were identified using R software and the competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed to identify the candidate circRNA-mediated aberrant signaling pathways. The hub genes were identified by MCODE and CytoHubba plugins of Cytoscape, and then a subnetwork regulatory module was established.

Results: A total of 27 circRNA-miRNA pairs and 208 miRNA-mRNA pairs, including 12 circRNAs, 24 miRNAs and 112 mRNAs were included in the ceRNA network. Subsequently, a subnetwork, including 4 circRNAs, 5 miRNAs and 6 mRNAs, was established based on related circRNA-miRNA-mRNA regulatory modules.

Conclusions: In summary, this work analyzes the characteristics of circRNA as competing endogenous RNA in AML pathogenesis, which would provide hints for developing novel prognostic, diagnostic and therapeutic strategy for AML.

Keywords: Acute myeloid leukemia; CircRNA; Competing endogenous RNA.

Fig. 1

Heatmap of the fifteen differentially expressed circRNAs from the two microarray datasets

Fig. 2

The circRNA-miRNA-mRNA network in the AML. Diamonds indicate circRNAs, rectangles indicate miRNAs, and ellipses indicate mRNAs. The red and blue nodes represent up-regulation and down-regulation, respectively

Fig. 3

Basic structural patterns of the twelve circRNAs

Fig. 4

Significantly enriched top 10 GO terms and KEGG analysis pathways of DEmRNAs involved in ceRNA network. a biological process; b cellular component; c molecular function and d KEGG signaling pathways

Fig. 5

Protein-protein intersection (PPI) network analysis of DEmRNA involved in the ceRNA network

Fig. 6

Validation and survival analysis of the six hub genes. a The mRNA expression level of six hub genes derived from TCGA database and GTEx projects. b The overall survival analysis of HGF and LDLR which are significantly related to the overall survival (OS) of patients with AML (P < 0.05)