MicroRNAs and their target gene networks in breast cancer

Abstract

MicroRNAs (miRNAs) are a major class of small endogenous RNA molecules that post-transcriptionally inhibit gene expression. Many miRNAs have been implicated in several human cancers, including breast cancer. Here we describe the association between altered miRNA signatures and breast cancer tumorigenesis and metastasis. The loss of several tumor suppressor miRNAs (miR-206, miR-17-5p, miR-125a, miR-125b, miR-200, let-7, miR-34 and miR-31) and the overexpression of certain oncogenic miRNAs (miR-21, miR-155, miR-10b, miR-373 and miR-520c) have been observed in many breast cancers. The gene networks orchestrated by these miRNAs are still largely unknown, although key targets have been identified that may contribute to the disease phenotype. Here we report how the observed perturbations in miRNA expression profiles may lead to disruption of key pathways involved in breast cancer.

Figure 1

Gene interaction network analysis of miRNA targets in breast cancer. Determined using Ingenuity software, the direct interaction network of 34 published targets of 11 miRNAs implicated in breast cancer pathogenesis is shown: miR-206 (grey), miR-17-5p (blue), miR-125a/b (cyan), miR-200 (dark green), let-7 (green), miR-34 (yellow), miR-31 (orange), miR-21 (pink), miR-155 (red), and miR-373/520c (maroon). The targets form a highly connected network centered on MYC. Arrows indicate protein-protein or protein-DNA interactions, suggesting these targets coordinate the expression and/or function of one another.