Negative Regulation Of β-catenin Signal Pathway By Pancreas Duodenum Homeobox-1

It is well known thatβ-catenin plays the key role in Wnt signal pathway. The exogenous expression of c-Myc, the target gene ofβ-catenin signal pathway, dramatically reduced the level of insulin in islet cells, which resulted in the serious diabetes followed with the death of mouse. PDX1 is essential for pancreatic development and islet function. Here we demonstrated that PDX1 could suppress c-myc promoter activity, which relied on TCF4 binding elements harbored in c-Myc promoter. PDX1 expression did not induceβ-catenin degradation nor did it alter their subcellular distribution. However, the expression of PDX1 leads to the reduction of P-catenin/TCF4/p300 complex levels and attenuates their binding activity with c-myc promoter sequences. Moreover, PDX1 functioned as a key regulator for proliferation, apoptosis and the maintenance of P cells function, at least in part, through controlling c-Myc expression. In addition, Laser Capture Microdissection (LCM) techniques and TaqMan miRNA assays specific for mature miRNAs were performed to assess the genomewide expression of miRNAs in human ICC. A cluster of 44 miRNAs was markedly distinguished unequivocally between ICC and normal cholangiocytes. Meanwhile, we identified that small number of differentially expressed miRNAs was correlated with specific ICC biopathologic features. Moreover, the exogenous expression of mir-320 or mir-204 could negatively regulate MCL-1 or BCL-2 expression and induce apoptosis to chemotherapy.