The miR-1-NOTCH3-Asef pathway is important for colorectal tumor cell migration.
The tumor suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumors. APC stimulates the activity of the Cdc42- and Rac1-specific guanine nucleotide exchange factor Asef and promotes the migration and invasion of colorectal tumor cells. Furthermore, Asef is overexpressed in colorectal tumors and is required for colorectal tumorigenesis. It is also known that NOTCH signaling plays critical roles in colorectal tumorigenesis and fate determination of intestinal progenitor cells. Here we show that NOTCH3 up-regulates Asef expression by activating the Asef promoter in colorectal tumor cells. Moreover, we demonstrate that microRNA-1 (miR-1) is down-regulated in colorectal tumors and that miR-1 has the potential to suppress NOTCH3 expression through direct binding to its 3'-UTR region. These results suggest that the miR-1-NOTCH3-Asef pathway is important for colorectal tumor cell migration and may be a promising molecular target for the treatment of colorectal tumors.
Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
Shiori
S
Furukawa
Yoshihiro
Y
Kawasaki
Masaya
M
Miyamoto
Masaya
M
Hiyoshi
Joji
J
Kitayama
Tetsu
T
Akiyama
D020413:3' Untranslated Regions / Q000235:genetics; D018938:Caco-2 Cells; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D020413:3' Untranslated Regions; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch