ZNF281-miR-543 Feedback Loop Regulates Transforming Growth Factor-β-Induced Breast Cancer Metastasis

Breast cancer is the most common malignancy, and metastasis is the main cause of cancer-associated mortality in women worldwide. Transforming growth factor-beta (TGF-beta) signaling, an inducer of epithelial-to-mesenchymal transition (EMT), plays an important role in breast cancer metastasis. Abnormal expression of miR-543 is associated with tumorigenesis and progression of various human cancers; however, the knowledge about the role of miR-543 in breast cancer metastasis is still unknown. In this study, we demonstrated that miR-543 inhibits the EMT-like phenotype and TGF-beta-induced breast cancer metastasis both in vitro and in vivo by targeting ZNF281. ZNF281 transactivates the EMT-related transcription factor ZEB1 and Snail. Furthermore, both ZEB1 and Snail can transcriptionally suppress miR-543 expression. Taken together, our data uncover the ZNF281-miR-543 feedback loop and provide a mechanism to extend the understanding of TGF-beta network complexity.