ZNF263 (Zinc finger protein 263)

DRD5P2 acts as a tumor suppressor in GC metastasis by suppressing Rock2/ERK/Snail signaling, and DRD5P2 is transcriptionally suppressed under hypoxia via the HIF-1α/ZNF263 axis.

While BCLAF1 recruits p85β to BCLAF1 loci, p85β facilitates the assembly of BCLAF1, the scaffold protein TRIM28 and the zinc finger transcription factor ZNF263, which together act in concert to activate BCLAF1 transcription. Collectively, this study provides functional evidence and mechanistic basis to support a role of nuclear p85β in modulating gene transcription.

ULK1 over-expressing ameliorated ZNF263 knockdown-induced inhibition of CRC proliferation. By activating the ULK1-autophagy axis, ZNF263 promotes proliferation of ICC and is potentially a prognostic or therapeutic target of ICC.

This promotion effect induced by the high expression of CPT1B on cisplatin resistance in LUAD was weakened after the addition of the FAO inhibitor Etomoxir. In summary, ZNF263 enhances cisplatin resistance in LUAD cells by upregulating CPT1B expression. This study enriches the molecular mechanisms of LUAD chemotherapy resistance and provides new directions for exploring therapeutic targets for LUAD.

Additionally, our study found that overexpression of ZNF263 enhanced the resistance of CRC cells to the chemoradiotherapy. In summary, this study not only elucidated the significant role of ZNF263 in CRC but also proposed novel approaches and methodologies for the diagnosis and treatment of this malignancy.

Notably, ZNF263 was identified as a putative prostate cancer TF with a significant impact on gene activity in the double-negative (AR- neuroendocrine-) subtype, potentially activating MYC targets. Overall, this analysis of chromatin accessibility in mCRPC provides valuable insights into epigenetic changes that occur during progression to mCRPC.

Finally, the coordination of ZNF263 and RNF126 promotes subcutaneous tumor size and distant liver metastasis in vivo. ZNF263, as an oncogene, promotes proliferation, drug resistance and EMT of PDAC through transactivating RNF126.

More importantly, lentivirus or adeno-associated virus (AAV)-mediated ZNF263 overexpression synergistically suppresses tumor growth and regrowth with osimertinib treatment in xenograft animal models. These findings suggest that enhancing ZNF263 may achieve complete response in LUAD with EGFR-targeted therapies.

This finding suggests that the inhibition of ZNF263 or IL33 may represent a novel therapeutic strategy for NSCLC. Importantly, our results highlight the crucial role of transcription factors in NSCLC and their potential as therapeutic targets.

We reveal that O-GlcNAcylation of Ser662 is responsible for the chromatin association of ZNF263 at candidate gene promoters and the OGT-facilitated HCC malignant phenotypes. Our data establish the importance of aberrant OGT activity and ZNF263 O-GlcNAcylation in the malignant progression of HCC and support the investigation of OGT as a therapeutic target for HCC.

Nearly one-third of ATAC-QTLs map to TF footprints and commonly altered DNA consensus motifs impacting chromatin accessibility include ETS family TFs (PU.1, SPI-B, ELF3, EHF), ZNF family (ZNF263, ZNF460) and CTCF. Collectively, using the largest B-ALL chromatin accessibility dataset to date, our investigation offers a unique window into the gene regulatory landscape that highlights the complexity and heterogeneity of chromatin accessibility among B-ALL molecular subtypes.