miR-30a Inhibits LOX Expression and Progression of Anaplastic Thyroid Cancer

Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies but its genetic drivers remain little understood. In this study, we report losses in expression of the microRNA miR-30a which is downregulated in ATC compared to differentiated thyroid cancer and normal tissue. miR-30a downregulation was associated with advanced differentiated thyroid cancer and higher mortality. Mechanistically, we found miR-30a decreased cellular invasion and migration, epithelial-mesenchymal transition marker levels, lysyl oxidase (LOX) expression and metastatic capacity. LOX was identified as a direct target of miR-30a that was overexpressed in ATC and associated with advanced differentiated thyroid cancer and higher mortality rate. Consistent with its role in other cancers, we found that LOX inhibited cell proliferation, cellular invasion and migration and metastasis in vitro and in vivo. Together, our findings establish a critical functional role for miR-30a downregulation in mediating LOX upregulation and thyroid cancer progression, with implications for LOX targeting as a rational therapeutic strategy in ATC.