Investigation Into The Mechanism Of REGgamma And Its Regulator In Tumoregenesis

REGy mediate the degradation of protein such as p21by proteasome and it is overexpressed in many tumors. But the mechanism of REGy in tumorigenesis and its regulation by different factors are still not fully understood. Here, we show REGy plays important roles in the prolifration, migration, dedifferention of tumorigenesis. Depletion of REGy not only decreased the proliferation, but also the migration of tumor cells. And the key molecule for migration, E-cadherin, and its regulator were upregulated. Moreover, the expression levels of many differention markers like NIS were increased as well in the cells after knockdown of REGy. Therefore, the uptake of idodine was enhanced in these cells. Ultilizing the thyroid orthotopic model, we found the survival duration of nude mice prolonged after knockdown of REGy. All these findings demonstrated the role of REG in tumorigenesis. Futhermore, we verified the impact of wild-type/mutant p53and TGFβ on REGy expression. Both wild type and TGFP can inhibted expression of REGy. Conversly, mutant p53can transactivate its expression. The level of REGy in HI299stable cells with mutant p53is higher compared with the cells with empty vector, but the level of p21is lower in such stable cells. Futher analysis proved mutant p53could atangonize TGF-β mediated gene regulation and thus, regulated many genes expression. These fingdings provided more knowledges about regulation of REGy expression and the the roles of mutant p53in tumorgenesis.