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.

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