Thyroid cancer has long been considered to arise in middle age and progress to more aggressive and lethal cancers after its repeated proliferation. In this research, we aimed at investigating the biological function and the underlying molecular mechanism of Melanoregulin (MREG) in thyroid cancer. It was found that the expression of MREG was significantly downregulated in thyroid cancer tissues. The downregulation of MREG expression was caused by epigenetic methylation. MREG overexpression could suppress the invasion and proliferation of thyroid cancer cells. While MREG knockdown promoted the invasion and proliferation of thyroid cancer cells. Furthermore, the phosphorylation of Akt or mTOR was decreased by MREG overexpression and increased by MREG knockdown. Moreover, Dactolisib (the inhibitor of mTOR) could abrogate silenced MREG induced thyroid cancer cell invasion and proliferation. Taken together, MREG regulates thyroid cancer cell invasion and proliferation through PI3K/Akt-mTOR signaling pathway. MREG may serve as a promising therapeutic strategy for thyroid cancer. (C) 2017 Elsevier Inc. All rights reserved.