Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells.
The insulin receptor substrate-1 (IRS-1), a docking protein for both the type 1 insulin-like growth factor receptor (IGF-IR) and the insulin receptor, is known to send a mitogenic, anti-apoptotic, and anti-differentiation signal. Several micro RNAs (miRs) are suggested by the data base as possible candidates for targeting IRS-1. We show here that one of the miRs predicted by the data base, miR145, whether transfected as a synthetic oligonucleotide or expressed from a plasmid, causes down-regulation of IRS-1 in human colon cancer cells. IRS-1 mRNA is not decreased by miR145, while it is down-regulated by an siRNA targeting IRS-1. Targeting of the IRS-1 3'-untranslated region (UTR) by miR145 was confirmed using a reporter gene (luciferase) expressing the miR145 binding sites of the IRS-1 3'-UTR. In agreement with the role of IRS-1 in cell proliferation, we show that treatment of human colon cancer cells with miR145 causes growth arrest comparable to the use of an siRNA against IRS-1. Taken together, these results identify miR145 as a micro RNA that down-regulates the IRS-1 protein, and inhibits the growth of human cancer cells.
Shi
Bin
B
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA.
Sepp-Lorenzino
Laura
L
Prisco
Marco
M
Linsley
Peter
P
deAngelis
Tiziana
T
Baserga
Renato
R
D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D035683:MicroRNAs / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics