Understanding Cancer Mutations by Genome Editing

摘要: The disco-interacting protein 2 homolog C (DIP2C) gene is an uncharacterized candidatebreast and lung cancer gene. contains a DMAP1 binding domain, pointing topotential involvement in DNMT1-dependent methylation. To study the role of DIP2C intumor development, we engineered human knockout cell systems by rAAV-mediatedgene targeting. Homo- heterozygous RKO cells displayed enlarged cellsand growth retardation. This phenotype was most pronounced DIP2C-/- knockouts, andthese also significant decrease mRNA levels. RNA sequencingrevealed 780 genes affected loss DIP2C, including cellular senescence markerP16INK4a. Functional annotation regulated shows enrichment involvedwith death processes, structure motility. Furthermore, KEGG pathway analysisshows association 19 with pathways cancer. In conclusion, phenotypic dataand expression changes induced indicate that function may beimportant for several biological processes implicated cancer, functionmay be trigger senescence.