O-GlcNAc transferase (OGT) catalyzes the addition of O-GlcNAc to certain serine or threonine residue on a wide variety of cytosolic and nuclear proteins and regulates cellular activities such as signaling and transcription. Although there are emerging evidences that OGT plays important roles in breast cancer metastasis, the underlying mechanism is not fully understood. In this study, we demonstrated that up-regulation of OGT correlates with breast cancer cells invasion. Over-expression of OGT stimulates cells invasion, while OGT silence exhibits the opposite effects. OGT is further identified as a target of microRNA24 (miR24). miR24 down-regulates OGT expression and subsequently suppresses cells invasion. Re-expression of OGT significantly rescues miR24-mediated invasion repression. Furthermore, our data showed that FOXA1 is subjected to O-GlcNAcylation, which instabilizes FOXA1 protein and promotes breast cancer cells invasion. In conclusion, our results demonstrated that miR24 inhibits breast cancer cells invasion by targeting OGT and reducing FOXA1 stability. These results also indicated that OGT might be a potential target for the diagnosis and therapy of breast cancer metastasis.
Keywords: Breast cancer; FOXA1; Invasion; OGT; miRNA24.
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