The Regulation Function Of REGγ On Anaplastic Thyroid Cancer

REGy protein which belongs to activators of the 20S proteasome, is mainly found in the nucleus, forms a homoheptamer to activate proteasome system and degrades some proteins in a Ubiquitin-independent and ATP-independent manner, and its substrates include SRC-3, p21,p16,CK-1δ,SirT1 and so on. REGγ is over-expressed in many cancer tissues, including colorectal cancer, lung cancer, gastric cancer and so on. There is also high expression of REGy in thyroid cancer, especially in anaplastic thyroid cancer. Anaplastic thyroid cancer is the most aggressive thyroid cancer, maintains in low differentiation status, and lacks effective treatments. So studying the regulating role of REGγ in anaplastic thyroid cancer is meaningful to illuminate the mechanism of anaplastic thyroid cancer tumorigenesis.We explored the roles of REGγ by focusing on its expression in thyroid carcinoma tissues, its effects on thyroid specific genes and so on, to clarify the function of REGγ during thyroid tumorigenesis. Results were that:REGγ was over-expressed in thyroid cancer tissues, REGγ inhibited expression of thyroid specific genes, promoted cell migration and proliferation; Besides, REGγ targeted Smurf2 for degradation, and Smurf2 could positively regulate thyroid specific genes, Smurf2 is negative regulator of TGFβ signal pathway, TGFβ could inhibit thyroid specific genes in a Smad3-dependent manner. All these data indicate that REGγ may be involved in the regulation of thyroid specific genes by enhancing TGFβ signaling.Anaplastic thyroid cancer is the most aggressive thyroid cancer, the median survival time of patients is only about half a year. So it has clinical meanings to illuminate the relationship between REGγ and anaplastic thyroid cancer. During the experiments, it was found that knocking down REGγ enhanced uptake of I131, which is critical in the clinical treatments, showing that REGγ may be a potential target in anaplastic thyroid cancer.