These results provided a mechanism for how the regulation of DFF45 signaling causes cancer cells to become sensitive to drug induced apoptosis. We also tested the e pression of p53 protein that is lost or mutated in more than half of all human cancers. p53 is a transcription factor that induces the e pression of miR 145 by interacting with a potential p53 response element in the miR 145 promoter. Additionally, in response to DNA damage, p53 interacts with the Drosha processing comple , and facilitates the processing of primary miR 145 to precursor miR 145. It is possible that the loss of p53 function may fail to stimulate miR 145 e pression. Consistently, precursor miR 145 or mature miR 145 was decreased in all colon tumor cells tested, all of which had down regulated Inhibitors,Modulators,Libraries wild type or mutant p53 protein.

Inhibitors,Modulators,Libraries Based on these results, an appealing hypothesis to e plain the miR 145 suppression observed in colon cancer cells is that it Batimastat is linked to a deficit in miRNA processing, and there is no relation between processing of primary miR 145 to pre cursor miR 145 and the p53 status. Together, our results define the role of miR 145 in the posttranscriptional regulation of DFF45, and suggest that miR 145 provides a possible link between p53 and DFF45 in this gene regulatory network. The potential use of a natural miRNA to sensitize cells to e ecute full blown apoptosis is e citing, and will hopefully lead to a new therapeutic strategy for the treatment of colon cancer. Conclusions Our study revealed a previously unrecognized function of miR 145 in DFF45 processing.

this function may underlie crucial aspects of cancer biology. This function may provide the possibility that the effect of chemother apeutics for human Inhibitors,Modulators,Libraries colon cancer may be improved by utilization of miR 145 in the near future. Methods and materials Tumor cells Inhibitors,Modulators,Libraries and materials Human colon cancer cells SW480, LS174T, SW620, COLO320DM and COLO205 were obtained from American Type Culture Collection. Normal colon cells were collected at Renji hospital, Shanghai, China. Fresh tissue samples were immediately put into liquid nitrogen, followed by primary culture in DMEM high glucose medium con taining antibiotics. MiR 145 mimic inhibitor was pur chased from Ambion. SYBR Premi E Taq was obtained from Takara Bio. DFF45 antibody and p53 antibody were purchased from ProteinTech Group Inc. SiRNA for DFF45 and control siRNA were purchased from GenePharma. Staurosporine was purchased from Sigma. Cell transfection Transfection of cells was performed with Lipofectamine 2000 Reagent following the manufacturers protocol. Briefly, the cells were seeded in 6 well plates at 30% confluence the day before transfec tion. MiR 145 mimic inhibitor and miRNA control, were used for each transfection.