miR-1226 targets expression of the mucin 1 oncoprotein and induces cell death.
The MUC1 oncoprotein is aberrantly overexpressed in human carcinomas and hematologic malignancies. Micro-RNAs (miRNAs) have been implicated in the suppression and induction of oncogenesis. The present studies demonstrate that the MUC1 mRNA 3' untranslated region (3'UTR) contains a highly conserved motif for binding of a novel miRNA, miR-1226, that has no known targets. The results show that miR-1226 is expressed in human breast cancer cell lines and non-malignant mammary epithelial cells. We also show that miR-1226 interacts with the MUC1 mRNA 3'UTR and that miR-1226 downregulates endogenous MUC1 protein levels. Consistent with miR-1226-induced downregulation of MUC1 expression, the results demonstrate that miR-1226 induces i) an increase in reactive oxygen species, ii) loss of the mitochondrial transmembrane potential, and iii) a decrease in cell survival. These findings indicate that expression of the MUC1 oncoprotein is downregulated by miR-1226 and that miR-1226 thereby functions as a tumor suppressor by promoting the induction of cell death.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Caining
C
Jin
Hasan
H
Rajabi
Donald
D
Kufe
D001483:Base Sequence; D001665:Binding Sites; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018396:Mucin-1 / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
C552310:MIRN1226 microRNA, human; D035683:MicroRNAs; D018396:Mucin-1; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species