Investigating the microRNA-mRNA regulatory network in acute myeloid leukemia

Haiguo Zhang; Chengfang Zhang; Rui Feng; Haixia Zhang; Min Gao; Ling Ye

doi:10.3892/ol.2017.6686

Investigating the microRNA-mRNA regulatory network in acute myeloid leukemia

Oncol Lett. 2017 Oct;14(4):3981-3988. doi: 10.3892/ol.2017.6686. Epub 2017 Jul 28.

Authors

Haiguo Zhang^{1

2}, Chengfang Zhang³, Rui Feng^{1

4}, Haixia Zhang⁵, Min Gao³, Ling Ye²

Affiliations

¹ Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
² Department of Hematology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China.
³ Department of Clinical Laboratory, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China.
⁴ Department of Hematology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
⁵ Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.

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.

Keywords: acute myeloid leukemia; differential expression; microRNA; regulatory network; reverse transcription-quantitative polymerase chain reaction; target genes.