Identifying the miRNA and mRNA‑associated networks to reveal potential prognostic biomarkers for Breast cancer

Backgrounds: Despite significant breakthroughs in breast cancer diagnosis and therapy, theprognosis remains unfavorable. MicroRNAs (miRNAs) appear to play a key role in the genesisand progression of human malignancies, according to mounting data. However, most miRNAs’regulation mechanisms and clinical relevance in breast cancer are yet unknown.Materials and Methods: The gene expression profiles for miRNA and mRNA were collectedfrom the Gene Expression Omnibus (GEO), in this study we systematically analyzed theexpression profiles of mRNA (GSE۵۴۰۰۲ dataset) and miRNA (GSE۴۲۵۲۵ dataset). UsingCytoscape, a miRNA-mRNA regulatory network was built and visualized. The STRINGdatabase was used to build the protein-protein interaction (PPI) network, and the cytoHubbaplugin was used to extract hub genes. The functions and signaling pathways associated withthese differentially expressed mRNAs were discovered using Gene Ontology and the KyotoEncyclopedia of Gene and Genomes.Results: We found ۲۲۵ differentially expressed miRNAs (DEmiRNAs), and ۶۶۵ DEmRNAs intotal. The enrichment results from analyzing DEmRNAs was shown to be associated withInteractions between immune cells and microRNAs in tumor microenvironment, B Cell ReceptorSignaling Pathway and Cancer immunotherapy by CTLA۴ blockade. Also construction of PPInetwork of the DEmRNAs showed ۵۶۴ nodes and ۳۸۹۹ edges in total from which one mostsignificant module was identified. We also selected the key deregulated miRNAs and mRNAsbased on statistical significance.Conclusion: Our results show the significant roles of miRNA-mRNA regulatory networks inbreast cancer and identified a new prognosis predictor and some potential prognostic biomarkersas well as involved genes and miRNAs in patients with breast cancer.

کلیدواژه ها:

Breast cancer ، GEO ، DEmiRNAs ، DEmRNAs ، microRNA