Comparative Analysis of microRNA Binding Site Distribution and microRNA-Mediated Gene Expression Repression of Oncogenes and Tumor Suppressor Genes

Abstract

MicroRNAs (miRNAs) are a family of short, noncoding RNAs that can regulate gene expression levels of over half of the human genome. Previous studies on the role of miRNAs in cancer showed overall widespread downregulation of miRNAs as a hallmark of human cancer, though individual miRNAs can be both tumor suppressive and oncogenic, and cancer genes are speculated to be more targeted by miRNA. However, the extents to which oncogenes and tumor suppressor genes (TSG) are controlled by miRNA have not been compared. To achieve this goal, we constructed lists of oncogenes and TSGs and compared them with each other, and with the whole protein-coding gene population, in terms of miRNA binding sites distribution and expression level changes upon genetic disruption of miRNA production. As expected, the results show that cancer gene mRNAs anchor more miRNA binding sites, and are under a higher degree of miRNA-mediated repression at both mRNA abundance and translation efficiency levels than the whole protein-coding gene population. Importantly, on average, TSG mRNAs are more highly targeted and regulated by miRNA than oncogene mRNAs. To the best of our knowledge, this is the first comparison of miRNA regulation of oncogenes and TSGs.