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.
La Rocca
Gaspare
G
Department of Cancer Biology at Thomas Jefferson University, Kimmel Cancer Center, Philadelphia, PA 19107, USA.
Shi
Bin
B
Badin
Margherita
M
De Angelis
Tiziana
T
Sepp-Lorenzino
Laura
L
Baserga
Renato
R
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D030541:Databases, Genetic; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction
D055504:Insulin Receptor Substrate Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1