hsa-miR-301a- and SOX10-dependent miRNA-TF-mRNA regulatory circuits in breast cancer.

Breast cancer is the most common cancer among women and the molecular pathways that play main roles in breast cancer regulation are still not completely understood. MicroRNAs (miRNAs) and transcription factors (TFs) are important regulators of gene expression. It is important to unravel the relation of TFs, miRNAs, and their targets within regulatory networks to clarify the processes that cause breast cancer and the progression of it. In this study, mRNA and miRNA expression studies including breast tumors and normal samples were extracted from the GEO microarray database. Two independent mRNA studies and a miRNA study were selected and reanalyzed. Differentially expressed (DE) mRNAs and miRNAs between breast tumor and normal samples were listed by using BRBArray Tools. CircuitsDB2 analysis conducted with DE miRNAs and mRNAs resulted in 3 significant circuits that are SOX10- and hsamiR-301a-dependent. The following significant circuits were characterized and validated bioinformatically by using web-based tools: SOX10→hsa-miR-301a→HOXA3, SOX10→hsa-miR-301a→KIT, and SOX10→hsa-miR-301a→NFIB. It can be concluded that regulatory motifs involving miRNAs and TFs may be useful for understanding breast cancer regulation and for predicting new biomarkers.