Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia

Abstract

Introduction:CircRNA is closely correlated with a wide variety of processes of acute myeloid leukemia (AML), whereas the novel circRNAs, their molecular mechanism and the specific function they played in AML should be explored in depth. Methods:The microarray chip data of AML patients and normal samples in the Gene Expression Omnibus (GEO) database were selected to differentially expressed (DE) circRNA, miRNA, and mRNA genes. The miRNA gene was the intersection of the circRNA target gene predicted using CSCD and the miRNA gene screened from AML patients, while the mRNA gene was the intersection of the target gene mRNA of miRNA predicted using miRanda and miRTarBase software and the mRNA gene screened from AML patients. The hub mRNAs related to survival were further screened through Cox proportional hazard regression. CircRNA/miRNA/ mRNA interaction network was constructed by using Cytoscape software.10 circRNAs and 6 miRNAs in bone marrow mononuclear cells (BMMNCs) of AML patients (n=43) and healthy controls (n=35) were determined by RT-qPCR. Correlations between them were analyzed by Pearson correlation coefficient. Results: 10 circRNAs, 6 miRNAs, and 33 mRNAs were identified. Subsequently, the network of circRNAs, miRNAs, and hub genes was built using Cystoscope. Four key circRNAs, seven hub genes and their regulatory pathways were identified. The result of RT-qPCRs showed that hsa_circ_0009581 and hsa_circ_0005273 were significantly upregulated in AML patients while hsa_circ_0000497 and hsa_circ_0001947 were significantly downregulated. Hsa-miR-150-5p was significantly downregulated; hsa-miR-454-3p was upregulated in AML patients. Hsa_circ_0009581 and hsa-miR-150-5p; hsa_ circ_0001947 and hsa-miR-454-3p were inversely correlated using Pearson's correlation coefficient. Conclusion:This study suggests that differentially expressed circRNAs take on a critical significance to AML development and may be the effective therapeutic targets. We suppose that hsa_circ_0009581 promotes leukemia development through hsa-miR-150-5p and hsa_circ_0001947 through hsa-miR-454-3p. hsa_circ_0001947 and hsa_circ_0009581 may provide new directions in the pathogenesis of AML.

Breakthrough treatment choice for Acute Myeloid Leukemia in pediatric and adult patients: Revumenib, an oral selective inhibitor of KMTA2Ar

“…2 Furthermore, existing research has suggested that circRNAs are capable of playing a role in the post-transcriptional regulation of AML by binding miRNAs, activating downstream signaling cascades, and regulating the expression of related genes, closely correlated with a wide variety of processes of AML. 7 AML has a poor prognosis and a considerable tendency to relapse 1 therefore, the need for effective treatment is undeniable.…”

Bioinformatics analysis of the potentially functional circRNA-miRNA-mRNA network in breast cancer

“…For example, in the bioinformatics study of Liu et al [ 5 ], it was emphasized that hsa_circRNA_0003638 may play a role in the pathogenesis of atrial fibrillation by targeting the CXCR4 gene via hsa-miR-1207-3p. Similarly, Hu et al [ 6 ] suggested that the interaction of hsa_circ_0009581 / hsa-miR-150-5p , and hsa_circ_0001947 / hsa-miR-454-3p may play a role in the AML cancer process. The precise biological classification of the BC subtype is critical for predicting the disease’s progression.…”

circ_HMGCS1 modulates hepatocellular carcinoma chemoresistance via miR‐338‐5p/IL‐7 pathway

“… 18 , 19 With the development of bioinformatics and sequencing technologies, increasingly circRNAs are found and reported to play important roles in various biological activities. 20 An increasing amount of evidence shows that circRNAs play an important role in HCC occurrence and development.…”