Project description:Differential gene expression analysis of MYCN-amplified neuroblastoma cells after transfection with Control siRNA, LYAR siRNA-6 or LYAR siRNA-10
Project description:Despite the identification of MYCN amplification as an adverse prognostic marker in neuroblastoma, MYCN inhibitors have yet to be developed. Here, by integrating evidence from a whole genome shRNA library screen and the computational inference of master regulator proteins, we identify Transcription Factor Activating Protein 4 (TFAP4) as a critical effector of MYCN amplification in neuroblastoma, providing a novel synthetic lethal target. We demonstrate that TFAP4 is a direct target of MYCN in neuroblastoma cells, and that its expression and activity strongly negatively correlate with neuroblastoma patient survival. Silencing TFAP4 selectively inhibits MYCN-amplified neuroblastoma cell growth both in vitro and in vivo, in xenograft mouse models. Mechanistically, silencing TFAP4 induces neuroblastoma differentiation, as evidenced by increased neurite outgrowth and up-regulation of neuronal markers. Taken together, our results demonstrate that TFAP4 is a master regulator of MYCN-amplified neuroblastoma and may represent a valuable novel therapeutic target.
Project description:We analyed the gene expression profiles after knocking down MYCN or TFAP4. Results showed that transcription factor MYCN and TFAP4 commonly regulats a subset of genes that may contribute to neuroblastoma cells proliferation and migration.
Project description:Differential gene expression in neuroblastoma cells after transfection with control siRNA, N-Myc siRNA-1, N-Myc siRNA-2, lncMycN siRNA-1 or lncMycN siRNA-2
Project description:Transcriptional profiling of long noncoding RNAs in human neuroblastoma BE(2)-C after transfection with control siRNA or N-Myc siRNA We analysed which long nocoding RNAs were N-Myc targets.
