Identification of six key miRNAs associated with breast cancer through screening large-scale microarray data.

Abstract

Breast Cancer (BC) is one of the most common primary malignant tumors, which is life threatening. Previous studies have demonstrated that microRNAs (miRNA) may regulate or affect the incidence of BC. However, results of these studies are inconsistent, due to factors including the different sequencing platforms and sample selection methods used. To explore the key miRNAs involved in the pathogenesis of BC, and to use these miRNAs to monitor the tumor progression of BC, a systematic review was performed on the previous studies examining BC miRNA; the function of the target genes that were modulated by these key miRNAs were also analyzed. A total of 8 representative miRNA datasets examining the pathogenesis of BC were selected. Key miRNAs were identified by comparing the overlap between these datasets. Then, the target genes of these key miRNAs were predicted through TargetScan. Furthermore, functional enrichment analysis of target genes and transcription factor (TF) binding analysis was also performed using the Database for Annotation, Visualization and Integrated Discovery and Tfacts database, respectively. A total of 6 key miRNAs were identified by comparing the differentially expressed miRNAs datasets in the pathogenesis of BC. Compared with normal tissues, 3 miRNAs were upregulated: Hsa-miR-21b; hsa-miR-29b; and hsa-miR-155; and 3 miRNAs were downregulated: Hsa-miR-10b; hsa-miR-125; and hsa-miR-145. The target genes regulated by the up- and downregulated miRNAs were significantly enriched in the biological processes of ‘transcriptional regulation’, and these target genes depended on RNA polymerase II promoter and DNA template, respective to the up- and downregulated genes. The downregulated key miRNAs were specifically enriched in the biological processes of ‘ephrin receptor signaling pathway’ (GO: 0048013) and ‘axon guidance’ (GO: 0007411). TF analysis of the key miRNA target genes revealed that 104 TFs interacted with the 319 target genes of the upregulated miRNAs, while the 92 TFs interacted with the 254 target genes of the downregulated miRNAs. In total, there were 133 TFs and 63 (47.3%) TFs shared by the 2 types (up- and downregulated) of target genes. In summary, 6 key miRNAs in BC were identified by systematic review; the corresponding target genes and TFs that bind to these target genes were also identified, and the potential functions of target genes were revealed. These data may be beneficial to increasing the accuracy of BC treatment through monitoring miRNA.