Investigating the microRNA-mRNA regulatory network in acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a common myelogenous malignancy in adults that is often characterized by disease relapse. The pathophysiological mechanism of AML has not yet been elucidated. The present study aimed to identify the crucial microRNAs (miRNAs/miRs) and target genes in AML, and to uncover the potential oncogenic mechanism of AML. miRNA and mRNA expression-profiling microarray datasets were downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed and a regulatory network between miRNAs and target genes was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to predict the biological functions of the differentially expressed genes. Reverse transcription-quantitative polymerase chain reaction analysis was employed to verify the expression levels of miRNAs and target genes in AML patient samples. A total of 86 differentially expressed miRNAs and 468 differentially expressed mRNAs between AML and healthy blood samples were identified. In total, 47 miRNAs and 401 mRNAs were found to be upregulated, and 39 miRNAs and 67 mRNAs were found to be downregulated in AML. A total of 223 miRNA-target genes pairs were subjected to the construction of a regulatory network. Differentially expressed target genes were significantly enriched in the Wnt signaling pathway (hsa04310), melanogenesis (hsa04916) and pathways in cancer (hsa05200). Significantly differentially expressed miRNAs and genes, including hsa-miR-155, hsa-miR-192, annexin A2 (ANXA2), frizzled class receptor 3 (FZD3), and pleomorphic adenoma gene 1 (PLAG1), may serve essential roles in AML oncogenesis. Overall, hsa-miR-155, hsa-miR-192, ANXA2, FZD3 and PLAG1 may be associated with the development of AML via the involvement of the Wnt signaling pathway, melanogenesis and other cancer-associated signaling pathways.

Bioinformatics Analysis Identifies Key Genes and Pathways in Acute Myeloid Leukemia Associated with DNMT3A Mutation

“…The KEGG enrichment analysis revealed that DEGs were enriched in pathways of cancer, PI3K-Akt signaling pathway, and transcriptional misregulation in cancer. Consistent with previous studies, the above pathways have been reported that affect the pathogenesis and prognosis of AML [ 30 – 33 ].…”

Identification of Key Genes and Pathways Associated with RUNX1 Mutations in Acute Myeloid Leukemia Using Bioinformatics Analysis

“…In this study, the KEGG enrichment analysis showed that DEGs were notably abundant in pathways of cancer, ECM-receptor interaction, and cAMP signal. While the cancer pathway was expected and is in line with a previous study [22], it is unclear how the ECM-receptor interaction pathway and the cAMP signaling pathway affect the pathogenesis and prognosis of AML. ECM-receptor interaction pathway enrichment was reported in esophageal squamous cell carcinoma [23].…”

The multiple ways Wnt signaling contributes to acute leukemia pathogenesis

“…These are a broad class of regulatory molecules, which comprises both long‐noncoding RNAs (lncRNAs) and small RNAs, like microRNAs (miRNAs). Two recent studies have tried to assess the contributions of these molecules to AML development and found that not only are they altered, but they also have an impact on prognosis 89,90 . Analyzing RNA‐seq public available data for AML, Pan et al.…”