A Systematic Analysis of miRNA-mRNA Paired Variations Reveals Widespread miRNA Misregulation in Breast Cancer

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNAs that can regulate gene expression by binding to target mRNAs and induce translation repression or RNA degradation. There have been many studies indicating that both miRNAs and mRNAs display aberrant expression in breast cancer. Previously, most researches into the molecular mechanism of breast cancer examined miRNA expression patterns and mRNA expression patterns separately. In this study, we systematically analysed miRNA-mRNA paired variations (MMPVs), which are miRNA-mRNA pairs whose pattern of regulation can vary in association with biopathological features, such as the oestrogen receptor (ER), TP53 and human epidermal growth factor receptor 2 (HER2) genes, survival time, and breast cancer subtypes. We demonstrated that the existence of MMPVs is general and widespread but that there is a general unbalance in the distribution of MMPVs among the different biopathological features. Furthermore, based on studying MMPVs that are related to multiple biopathological features, we propose a potential crosstalk mechanism between ER and HER2.