MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed in thyroid cancer. However, the role of miRNAs in thyroid cancer metastasis remains largely unknown. In the current study, we found that miR-539 plays a suppressor role in thyroid cancer cell migration and invasion. Luciferase reporter assays confirmed that miR-539 binding to the 3'-UTR region of CARMA1 inhibited the expression of CARMA1 in thyroid cancer cells. Further studies demonstrated that CARMA1 can significantly promote the migration and invasion of thyroid cancer cells. Interestingly, overexpression or knockdown of CARMA1 effectively blocked the effect of miR-539 on the migration and invasion of thyroid cancer cells. Furthermore, we showed that miR-539 expression was frequently downregulated and CARMA1 expression was significantly upregulated in thyroid cancer cell lines and thyroid cancer tissues compared with controls. Taken together, our data indicate that miR-539 is a novel regulator of migration and invasion in human thyroid cancer cells by targeting CARMA1. (C) 2015 Published by Elsevier Inc.