In silico analysis of hsa-miR-181a-5p target genes and rs9266 relation with acute myeloid -leukemia

In silico analysis of hsa-miR-181a-5p target genes and rs9266 relation with acute myeloid -leukemia
Anasik Karabedianhajiabadi,^1,* Fateme Abedi Dorcheh,² Setare Samizade,³ Alireza Nasr Isfahani,⁴
1. Department of Microbiology, School of Biological Sciences, Islamic Azad University of Falavarjan, Iran
2. Department of Biochemistry, School of Bioscience and Biotechnology, Shahid Ashrafi University of Sepahanshahr, Isfahan, Iran
3. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
4. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
Introduction: Each year, nearly 60,000 people are diagnosed with leukemia. The development risk of Acute Myeloid Leukemia (AML) is considered to be increased by age. Leukemia is being listed as a genetic disease; genes are reviewed as one of the causes of this disease. As people could inherit genetic factors, based on the researches, miRNAs (small non-coding RNAs) and SNPs (single nucleotide polymorphisms) might develop the chance of being infected by Leukemia. This study has been done in order to diagnose a potential biomarker for early detection of AML. According to bioinformatics analysis, hsa-mir-181a-5p, which is located on chromosome 9, was selected for this survey.
Methods: As this research was done based on bioinformatics analysis miRbase, miRTarbase, miRWalk, TargetScan, DIANA TOOLS, DAVID, miRdSNP, miRNASNP, miRSNPdb, GeneMANIA databases and Cytoscape 3.8.0 software were needed to get proper data of micoRNA basis, validated and predicted target genes, gene's expressions, signaling pathways, SNP and genes' interaction networks.
Results: According to the hsa-mir-181a-5p targets PDPK1, AKT3, HRAS, SOS1, MAPK1, MAP2K1, PTEN, PIK3CB, PIK3R3 genes are considered as the most frequent genes of FoxO, PI3K-AKT and Focal adhesion signaling pathways of Acute Myeloid Leukemia which their similar pattern is clearly notable. Furthermore, in the bioinformatics analysis of this study, the occurrence of rs9266 in KRAS, one of the AML disease genes, showed to have vital role in AML disease process, but to understand the role of this SNP in AML a wide range of surveys are required.
Conclusion: According to PI3K-AKT signaling pathway, some genes, including MAP2K1, MAPK1, BCL2, CDKN1B, HRAS seem might lead to metastasis via causing cell proliferation, angiogenesis. Moreover, in Focal adhesion pathway, MAPK8 gene which activates via a cascade of genes, is able to trigger cell proliferation. Thus, inhibition of these genes by hsa-mir-181a-5p that lead to metastasis and proliferation, mentioned miRNA is considered to be tumor suppressive.
Keywords: Bioinformatics, miRNA, SNP, AML, Signaling pathway