The Regulation Mechanism Of REGgamma For Anaplastic Thyroid Cancer Through Smad7?Smurf2

REGgamma protein is a kind of factor which can activate proteasome,it mainly exists in the nucleus,belongs to the 20s proteasome activation factor family,its pathway of degradation of the protein depends neither on ubiquitin nor ATP,so far we have found the SRC-3,p21,p16,CK-1 the delta,SirTl can be its substrate.Researches have shown that REGgamma in the stomach,lung and colon cancer tissue has a high level of expression,and Anaplastic Thyroid Cancer(ATC)is the most dangerous cancer and it has the highest malignant degree,at the same time,the cure rate of ATC remains lowest among all the thyroid cancers.This paper mainly studied about the regulation of REGgamma for ATC.So the research is of great significance.We used two kinds of ATC cells,SW1736 and K18 cells,when REGgamma was knocked down,to compare the expressions of Thyroid specific genes,for example,TTF-1?TTF-2,and so on.At the same time,comparing with Smad3 and Smad4,Smurf2,Smad7,etc,which can regulate TGFbeta signaling pathway,and then we found that in REGgamma knockdown cells,all kinds of thyroid specific genes had an increase in amount.And we also found that CTGF?Smad7?PAI-1,which were TGFbeta signaling pathways downstream target genes,had different amounts in ATC cells.So we get the conclusion that REGgamma can positively regulate TGFbeta signaling pathways.Then we studied TGFbeta signaling pathway,and we found Smurf2 as a key protein.Its expressions in ShN and ShR cells had tiny difference,since we had proved that REGgamma could influence TGFbeta signaling pathway,and TGFbeta signaling pathway could influence thyroid specific genes,we had reported the anaplastic thyroid cancer cells,so we used si-Smurf2 to transfect two kinds of ATC cells,we found that the decreases of Smurf2 could inhibit the thyroid specific genes,so Smurf2 is the key protein which can influence the regulation of Thyroid specific genes.And we know that Smad7 is a target gene in the downstream of TGFbeta signaling pathway,and Smurf2 can bind to Smad7,then we compared the expression of Smad7 in SW1736 cells and K18 cells when REGgamma knocked down.And we could see the inhibition was obvious.Then we also found that Smad7 could bind to Smurf2,and this means that Smad7 is another key protein in the regulation of REGgamma for ATC.In this paper,the main point is that we found two key regulatory proteins:Smad7 and Smurf2,these two proteins may be the key point of regulation of REGgamma for Anaplastic Thyroid Cancer.Increasing the expressions of thyroid specific genes by REGgamma and the ability to assimilate iodine,therefore REGgamma may become the anew target to cure the ATC,and it may be a gospel for anaplastic thyroid cancer patients.