The Intricate Interplay between the ZNF217 Oncogene and Epigenetic Processes Shapes Tumor Progression

Simple Summary The ZNF217 oncogene promotes progression, pluripotency and resistance to therapy in different types of cancer and is associated with increased risk of metastasis. High ZNF217 expression levels are a biomarker of poor prognosis in several cancers. Therapies targeting ZNF217 could be promising in cancer treatment; however, the lack of identification of the full 3D structure of ZNF217 incites investigation of mechanisms of regulation of ZNF217 to delineate alternative candidate therapeutic strategies. In fact, studies show that ZNF217 shapes cancer growth through epigenetic mechanisms that promote tumor progression, including DNA methylation, interactions with noncoding RNAs and epitranscriptome refining, which are summarized in this review. We also discuss how it would be promising to assess noncoding RNAs that regulate ZNF217 expression and function, as well as to investigate the DNA methylation status of ZNF217 locus, as biomarkers of poor prognosis and to monitor therapeutic response to treatment. The oncogenic transcription factor ZNF217 orchestrates several molecular signaling networks to reprogram integrated circuits governing hallmark capabilities within cancer cells. High levels of ZNF217 expression provide advantages to a specific subset of cancer cells to reprogram tumor progression, drug resistance and cancer cell plasticity. ZNF217 expression level, thus, provides a powerful biomarker of poor prognosis and a predictive biomarker for anticancer therapies. Cancer epigenetic mechanisms are well known to support the acquisition of hallmark characteristics during oncogenesis. However, the complex interactions between ZNF217 and epigenetic processes have been poorly appreciated. Deregulated DNA methylation status at ZNF217 locus or an intricate cross-talk between ZNF217 and noncoding RNA networks could explain aberrant ZNF217 expression levels in a cancer cell context. On the other hand, the ZNF217 protein controls gene expression signatures and molecular signaling for tumor progression by tuning DNA methylation status at key promoters by interfering with noncoding RNAs or by refining the epitranscriptome. Altogether, this review focuses on the recent advances in the understanding of ZNF217 collaboration with epigenetics processes to orchestrate oncogenesis. We also discuss the exciting burgeoning translational medicine and candidate therapeutic strategies emerging from those recent findings connecting ZNF217 to epigenetic deregulation in cancer.

Automated summary

ZNF217 oncogene promotes cancer progression, pluripotency and resistance to therapy. High expression levels of ZNF217 are associated with poor prognosis in several cancers. ZNF217 shapes cancer growth through epigenetic mechanisms, including DNA methylation, interactions with noncoding RNAs, and epitranscriptome refining. Noncoding RNAs and DNA methylation status of ZNF217 locus can be potential biomarkers for poor prognosis and therapeutic response.