REG? Induces The Formation Of Anaplastic Thyroid Cancer Through TGF? Signal Pathway

Anaplastic Thyroid Cancer(ATC)is a kind of thyroid cancer with high mortality.Since the incidence is gradually rising and therapeutic effect is constantly terrible,individuals increasingly concerntate on this tumor.The most reason of high death rate in ATC without expression of NIS is the failure of radioiodide therapy.REGy,also named 20S proteasome activator,can participate in the process of protein degradation which is an ATP-independent and Ubquitin-independent manner,such as SRC-3/AIB1,p21 and CK-1.Now,numerous researches detected the relationship between the high expression of REGy and tumorigenesis.Our project mainly explore whether REGy has effect on the formation of anaplastic thyroid cancer or not.At the beginning,we found REGy can inhibit the expression of thyroid specific genes,such as NIS,Pax8 and TTF-1.Afterwards we confirmed REGy regulated these specific genes through TGF? signal pathway to induce the tumorigenesis.Finally,it is interesting that the increase of REGy probably reduced the level of smad7.Consequently,we describe a novel molecular menchanism about forming ATC.Because of our discovery that knock-down REGy rescue the expression of thyroid specific genes,especially NIS,it will partly improve the effect of radioiodide therapy.Our perspective that the death rate of ATC would decrease by interfering REGy exprssion is greatly significant for clinical treatment.Besides,REGy will probably become a potential therapeutic target to alert the level of differentiation of ATC.In this dissertation,we provide a theoretical envidence for resolving above-mentioned problems.