MicroRNA-206 targets notch3, activates apoptosis, and inhibits tumor cell migration and focus formation.
MicroRNAs contribute to cancer development by acting as oncogenes or tumor suppressor genes. However, only a few microRNA target genes were determined. We identified a nearly perfect complementarity between miR-206 and the 3'-untranslated regions of both mouse and human notch3. Expression of miR-206 decreased the luciferase activity dose-dependently when cotransfected with the mouse or human notch3 3'-untranslated region-luciferase reporter containing the miR-206 target site in HeLa cells. This suppression was relieved by deletion and mutation of the miR-206-binding site and was partially recovered by expression of notch3 or by a specific inhibitor of miR-206. Interestingly, overexpression of miR-206 decreased the levels of both Notch3 protein and mRNA. Expression of miR-206 markedly induced apoptotic cell death and blocked the anti-apoptotic activity of Notch3. In addition, ectopic expression of miR-206 inhibited HeLa cell migration and focus formation. Therefore, we identified miR-206 as a pro-apoptotic activator of cell death, which was associated with its inhibition of notch3 signaling and tumor formation. The inhibition of cancer cell migration and focus formation by miR-206 strongly suggests that miR-206 may function as a novel tumor suppressor.
Song
Guisheng
G
Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Zhang
Yuxia
Y
Wang
Li
L
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014945:Wound Healing
D020413:3' Untranslated Regions; D035683:MicroRNAs; C499374:NOTCH3 protein, human; C499373:Notch3 protein, mouse; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D008156:Luciferases