Identifying MicroRNA-mRNA regulatory network in breast cancer sample with drug resistance

Introduction: MicroRNAs (miRNAs) are involved in tumor progression by regulating post-transcriptional gene expression. However, the relationship between miRNAs and target genes and miRNA-mRNA regulatory network in breast tumorigenesis is poorly studied. The aim of this study is to identify the Breast cancer (BC) specific miRNAs and their target mRNAs in Drug resistance pathway using a multi-step approach. Methods: A multi-step method merging microarray expression profile (GSE24460, GSE62259) andbioinformatics study was implemented to identify the BC specific miRNA-mRNA regulatory network. First, 69 differentially expressed miRNAs and 3832 mRNAs from BC samples compare with normal sample and MCF7 resistance cell were identified by microarray data analysis in Expression Console software (Affymetrix) and FlexArray software. Then, about 30 dysregulated miRNAs and their 68 target mRNAs were identified by a combination of analysis and prediction by TargetScan and mirwalk. The miRNA gene regulatory network was revealed by Cytoscape software. Results: Bioinformatics analysis displayed that these miRNA-mRNAs were involved in Wnt signaling andMDR pathway. Also 38 tumor suppressor genes identified that down-regulated in analysis. Furthermore, 5 up-regulated miRNAs (mir-19a, mir-218, mir-200c, mir-99a, and mir-27a) and 4 down-regulated predicted target mRNAs (Wnt5A, TSC1, ATXN1, CYP24A1) with upper score were selected. Finally, functional analysis was performed for the target genes followed by construction of a miRNA‑target gene network. Conclusions: The results in our study may be useful to further research to understand the underlyingregulatory mechanisms of miRNA and their target genes in BC that may be new goals for breast cancer therapy.

Keywords:

MicroRNAs , Target mRNAs , Regulatory network , breast cancer , drug resistance