An Investigation On The Mechanism Of TXNIP(Thioredoxin-Interacting Protein) As A Tumor Suppressor

In tumor cells,the expression of TXNIP is significantly down-regulated,and many studies have shown that TXNIP is a potential tumor suppressor,but the mechanism remains unknow.The protein tagged with GFP was found to be located in the nucleus,and further studies showed that TXNIP could be located in Cajal Bodies and nucleoli.In this study,based on the location of TXNIP in the nucleus,the anti-cancer mechanism of TXNIP is explored from the two aspects:the effect of TXNIP on histones' and rRNAs'expression.The results showed that:compared with normal tissues,TXNIP expression was significantly reduced in colorectal lesions tissues.Clone formation showed that the overexpression of TXNIP could inhibit cell proliferation.After the overexpression of TXNIP,the cell cycle was blocked in the G1 phase,preventing the cells from entering the S phase to express histones.TXNIP may also affect histones' expression by inhibiting NPAT,which controls histone synthesis.In addition,CHIP assays showed that TXNIP was able to bind to various histone promoters,and the dual-luciferase reporter assay further demonstrated that the binding of TXNIP to histone promoters inhibited histone promoter activity.Similarly,CHIP assays also showed that TXNIP was able to bind to the promoter of rDNA.These results suggest that TXNIP plays an important role in inhibiting histone gene expression and rRNA gene expression,thereby affecting cell growth.This study aims to provide new ideas for the treatment of cancer by exploring the mechanism of TXNIP against cancer.