MicroRNA-1229 overexpression promotes cell proliferation and tumorigenicity and activates Wnt/ß-catenin signaling in breast cancer.

ABSTRACT

Constitutive activation of the Wnt/ß-catenin pathway promotes malignant proliferation and it is inversely correlated with the prognosis of patients with breast cancer. However, mutations in key regulators, such as APC, Axin and ß-catenin, contribute to aberrant activation of the Wnt/ß-catenin signaling pathway in various cancers, but rarely found in breast cancer, suggesting that other mechanisms might be involved in the activation of Wnt/ß-catenin signaling in breast cancer. In the present study, we found that miR-1229 expression was markedly upregulated in breast cancer and associated with poor survival. Overexpressing miR-1229 promoted while inhibiting miR-1229 reduced, proliferation of breast cancer cell proliferation in vitro and tumor growth in vivo. Furthermore, we found that overexpression of miR-1229 activated the Wnt/ß-catenin signaling pathway in breast cancer by directly targeting the multiple important negative regulators of Wnt/ß-catenin signaling, including adenomatous polyposis coli (APC), glycogen synthase kinase-3ß (GSK-3ß), and inhibitor of ß-catenin and T cell factor (ICAT). Taken together, our results suggest that miR-1229 plays an important role in promotion breast cancer progression and may represent a novel therapeutic target in breast cancer.