ZNF643/ZFP69B exerts oncogenic properties and associates with cell adhesion and immune processes [ChIP-seq]
The global cancer burden remains high; thus, it is crucial to entangle molecular mechanisms driving carcinogenesis to improve current prevention and treatment options. We previously detected the ZNF643/ZFP69B gene upregulated in multiple tumors, and we speculated it may play a role in tumor biology. To test this hypothesis, we employed TCGA-centered databases to correlate ZNF643 status with various clinicopathological parameters. We also performed RNA-seq analysis, in vitro studies assessing cancer cell phenotype, and searched for ZNF643-bound genomic loci. Our data indicated higher levels of ZNF643 in most analyzed tumors compared to normal samples, possibly due to copy number variations. ZNF643 mRNA correlated with diverse molecular and immune subtypes and clinicopathological features (tumor stage, grade, patient survival). RNA-seq analysis revealed that ZNF643 silencing triggers the deregulation of the genes implicated in various cancer-related processes, such as growth, adhesion, and the immune system. Moreover, we observed that ZNF643 positively influences cell proliferation, cell cycle, migration, and invasion in a cell type-dependent manner. Finally, our ChIP-seq analysis indicated that the genes associated with ZNF643 binding are linked to adhesion and immune signaling. In conclusion, our data confirm the oncogenic properties of ZNF643 and pinpoint its impact on cell adhesion and immune processes. Overall design: Chromatin immunoprecipitation coupled with next generation seqencing (ChIP-seq) with anti-HA antibody in wild-type (WT) and HA-tagged ZNF643 overexpressing SKMES lung cancer cell line.