Akademik Veri Yönetim Sistemi
Istanbul Tip Fakultesi Dergisi, cilt.86, sa.1, ss.59-68, 2023 (Scopus)
Objective: Acute myeloid leukemia (AML) is a deadly type of leukemia. The expression of AML-related genes may be altered not only by genetic changes but also by various epigenetic factors such as microRNAs (miRNAs). The expression levels of many genes can be altered by miRNAs. The detection of miRNA's target genes is critical for an understanding of the disease's molecular mechanism. In this study possible target genes of miR-34a-5p in AML were determined and the effect of the relationship between miR-34a-5p and target genes on the cancer process was investigated. Materials and Methods: Leukemia Gene and Literature Database web tool (http://soft.bioinfo-minzhao.org/lgl/) includes a useful leukemia gene and literature da. There are more than 600 AML-related genes on this database. In the present study, in order to define the potential target genes of miR-34a-5p on the database, we used miRDB tool and then confirmed the findings using miRWalk, miRTarbase, Tarbase and miRNet tools. Defined miR-34a-5p AML related genes were verified by the DisGeNET platform. A Protein-Protein Interaction (PPI) network analysis of the genes was conducted using several bioinformatics tools. The effect of miR-34a-5p on cell proliferation was investigated by transfecting mimic miR-34a-5p into HL60 and NB4 cells. The mRNA expressions of NOTCH2, IGF1R, SKP2 and CDC25A genes were investigated in miR-34a-5p transfected NB4 and HL60 cells and control groups. Results: Using bioinformatics tools we determined 44 AML-related genes that could be targeted by miR-34a-5p. According to our in vitro study results statistically significant suppression of proliferation was observed in miR-34a-5p transfected cells (48h HL60 cells p=0.00011; NB4 cells p=0.0031 and 96h HL60 cells p=0.00013; NB4 p=0.00018). It was also found that NOTCH2, IGF1R, SKP2 and CDC25A mRNA expressions were downregulated in miR-34a-5p mimic-transfected HL60 cells (p=0.003; p=0.02; p=0.01; p=0.0009 respectively) and NB4 cells (p=0.02; p=0.02; p=0.01; p=0.0007 respectively) compared to the control groups. Conclusion: miR-34a-5p may inhibit AML cell proliferation by targeting many genes like NOTCH2, IGF1R, SKP2 and CDC25A. The results of our study indicate that appropriate bioinformatics tools and in vitro methods can successfully be used together when investigating the relationship between miRNAs and target genes. Further studies are required to determine the detailed relationship between these genes and miR-34a-5p.