WDR77 (WD Repeat Domain 77)

Moreover, fludarabine targeting STAT1 in combination with anti-PD-1 has a synergetic effect on suppressing tumor growth in mice. Overall, this study reveals that the RNA binding-dependent function of PRMT5 regulates PDCD1 and T cell effector function with WDR77 and identifies potential combinatorial therapeutic strategies for enhancing antitumor efficacy.

Overexpression of WDR77 also increased CDC20 protein levels. WDR77 serves as both a prognostic biomarker and functional regulator in melanoma, highlighting its potential as a therapeutic target.

Furthermore, our ML model achieved an accuracy of 89.58% to predict patient survival. The clinical and biological features proposed here in conjunction with ML can improve the interpretation of CRC mechanisms and predict patient survival.

In addition, analysis of interpretability using attention revealed the major subtype-specific biomarkers, including UBA2, LRRC41, ANKRD53, and WDR77, that show great biological relevance and could be used as diagnostic and therapeutic tools. The proposed multi-omics based on a biological and explainable framework provides a solid computational approach to molecular stratification and biomarker identification in lower-grade glioma, bridging between predictive power, biological clarification, and clinical benefits.

Blocking AR-WDR77 cooperation also delayed the growth of organoids from patient-derived xenografts and fresh CaP specimens. Disrupting coregulator control over AR action may thus improve survival from ADT-resistant CaP.

Finally, we outline key challenges and future directions in translating PRMT5:MEP50 PPI inhibitors into clinical settings, emphasizing the importance of biomarker-guided patient selection, combination therapy strategies, and optimization of drug pharmacokinetics. Together, these insights underscore the therapeutic promise of targeting the PRMT5:MEP50 interaction as a next-generation approach to precision epigenetic cancer therapy.

Gene co-expression analysis demonstrated a high correlation between WDR77 and glioma cell cycle, metabolism, and immune processes. Overall, we identified WDR77 as a new biomarker closely associated with the malignant phenotype and poor prognostic outcomes for glioma, playing an important role in regulating the cell cycle and immune processes.

GATA3 and E2F6 directly interact with the promoter of the WDR77 gene in vitro and in vivo and repress WDR77 promoter activity. These results provide valuable insights into the molecular mechanisms governing WDR77 expression during prostate development and prostate tumorigenesis.

This dual function makes WDR77 an attractive therapeutic target, as disrupting its interactions with critical signaling pathways or modulating its translocation could yield novel strategies for cancer treatment. Given WDR77's role in oncogenic pathways independent of PRMT5, further exploration of WDR77 and its non-PRMT5-related activities may reveal additional therapeutic opportunities in an array of cancers.

Moreover, depletion of PRMT5 and WDR77 repress SCC in vivo. This study reveals for the first time that PRMT5 and WDR77 synergize to promote SCC proliferation via the ΔNp63α-p21 axis, highlighting a novel therapeutic target for SCC.

This interaction enhances the methyltransferase activity of PRMT5, leading to increased AKT phosphorylation activation and promotion of breast cancer cell proliferation. In conclusion, this study uncovers a novel function of TBL2 in the activation of AKT by PRMT5 and suggests TBL2 as a potential therapeutic target for BC treatment.

WDR77 holds potential as an oncogene and biological marker in various cancers, particularly CRC.