ABSTRACT: Despite the ongoing progress in diagnosis and treatments, cancer remains a threat to more than one-third of the human population. It is a complex disorder characterized by multi-omic aberrations affecting cell proliferation, death, migration, plasticity, interaction with the immune system, and other features. The emerging data indicate that many KRAB-ZNF factors belonging to a large gene family may be involved in carcinogenesis. Our previous study identified ZNF714, a KRAB-ZNF gene of unknown function, as commonly overexpressed in many tumors, pointing to its hypothetical oncogenic role. Here, we harnessed the TCGA-centered online databases, performed functional studies and transcriptomic and methylomic profiling to test this hypothesis, and explore ZNF714 function in cancer. Our pan-cancer analyses confirmed that ZNF714 is frequently upregulated in multiple tumors, possibly as a result of regional amplification, promoter hypomethylation, and NFYB signaling. We also showed that ZNF714 expression correlates with tumor immunosuppressive features. The in vitro studies indicated that ZNF714 expression positively associates with proliferation, migration, and invasion. In line with these observations, the transcriptomic analysis of ZNF714 knocked-down cells demonstrated deregulation of cell adhesion, migration, proliferation, apoptosis, and differentiation. Importantly, we provided evidence that ZNF714 negatively regulates the expression of a number of known TSGs via promoter methylation. However, as ZNF714 did not show nuclear localization in our research model, the regulatory mechanisms exerted by ZNF714 require further investigation. In conclusion, our results reveal, for the first time, that ZNF714 may have oncogenic functions.
