A Microarray Profile of Triple Negative Breast Cancer related to onco-miRNAs and Their Target Genes
A Microarray Profile of Triple Negative Breast Cancer related to onco-miRNAs and Their Target Genes
Zahra Torki,1,*Mohammad Reza Alivand,2
1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Introduction: Triple negative breast cancer (TNBC), a subtype of breast cancer characterized by its aggressive nature, has higher lethality rates in affected women among other types of breast cancer. It has been shown that microRNAs (miRs) are associated with the progression of TNBC, since these molecules can affect the expression levels of their target genes and control specific pathways as a result. Here we focused on detecting dysregulation of miRs and their target genes in TNBC.
Methods: First, the gene expression omnibus (GEO) database was searched for microarray studies using TNBC samples and control samples. We searched for datasets that employed the miR and mRNA platforms in their research designs. After data analysis based on the limma packages methodology, the second step involved the discovery of deregulated miRs and mRNAs using the web program GEO2R. The filter for determining the differentially expressed miRs/mRNAs (DEMs/DEGs) was applied (|logFC| > 2 and pvalue < 0.5), and only up regulated DEMs were selected for further target gene detection using bioinformatics analysis. Thirdly, only down regulated DEGs that were also in common with the predicted target genes of the DEMs were selected for pathway detection, gene ontology (GO) and protein network analyses as well as expression validation on UALCAN data base.
Results: One miR related microarray study (GSE154255) and two microarray studies using gene expression profiling platforms (GSE113865 and GSE65216) have entered in this study. Following the filtration, the GSE154255 included 33 DEMs with 9 miRs that were up expressed and 23 miRs that were downregulated. The target genes of all the 9 upregulated DEMs (hsa-miR-590-5p, hsa-miR-182-5p, hsa-miR-183-5p, hsa-miR-18a-5p, hsa-miR-18b-5p, hsa-miR-491-3p, hsa-miR-362-3p, hsa-miR-301a-3p and hsa-miR-7-5p) that were matched with the list of down expressed mRNAs in TNBC microarray datasets contained 2755 genes in total. The MAPK signaling pathway was the one that was most substantially enriched in TNBC, according to KEGG pathway analysis.
Conclusion: Altogether, through using an in silico method, this study showed hsa-miR-590-5p, hsa-miR-182-5p and hsa-miR-18b-5p had the highest expression levels in TNBC samples.