Growth inhibition by microRNAs that target the insulin receptor substrate-1.

We have examined several microRNAs (miRs) indicated by the databases as targeting the signaling pathway of the type-1 insulin-like growth factor receptor (IGF-IR). Most of the miRs tested had multiple targets, as expected, leading to cell death. However, miR145 seemed to affect its tumor suppressor activity largely by downregulating the docking protein of the IGF-IR, the insulin receptor substrate-1 (IRS-1). These results suggest that, despite the many targets provided by the databases, in some cases a single target can be predominant in determining the end results.