WDR4 (WD Repeat Domain 4)

Single-cell analyses reveal tumor- and cell-type-specific expression patterns of RMEs, while supportive functional data suggest a potential biological relevance of NAT10 in HCC. Collectively, these findings provide an association-based framework for understanding the potential roles of RNA modification programs in cancer progression and clinical stratification.

Moreover, METTL1 shapes the tumor immune microenvironment by modulating immune cell infiltration, promoting immunosuppressive populations, and contributing to immune evasion, which has implications for immunotherapy. Collectively, METTL1 functions as a pivotal driver of cancer progression and represents a promising biomarker and therapeutic target, highlighting the potential of targeting tRNA m7G modification in precision oncology.

Targeted silencing of WDR4 in TAMs using a CpG-small interfering RNA delivery system enhances antitumour immunity, inhibits tumour progression and improves the efficacy of anti-PD-1 therapy. Our findings identify WDR4 as a key regulator of TAM polarization and a promising therapeutic target to enhance immunotherapeutic outcomes.

The oesophagus cancer line OE33 shows no proliferative defect upon METTL1/WDR4 loss, despite complete lack of m 7 G46 on its tRNA. OE33 coordinates codon usage and abundance of cognate tRNAs in the absence of METTL1/WDR4; the METTL1/WDR4 sensitive line, OE21, fails to do so.Depleting dihydrouridine synthases (DUS-L) renders OE33 sensitive to METTL1/WDR4 loss.OE33 responds to lack of METTL1/WDR4 activity by upregulating DUS3L and its activity (D47) on tRNA; the sensitive line OE21 fails to do so.METTL1-sensitive lines have intrinsically low DUS3L and cannot sustain higher levels.DUS3L reveals as a potential biomarker for METTL1 sensitivity.

In conclusion, WDR4 is highly expressed in glioma and promotes tumor progression via the PI3K/Akt-CDK1/2 signaling axis. These findings indicate that WDR4 may serve as a potential prognostic biomarker and therapeutic target in glioma.

m7G-driven selective regulation exerts context-dependent, two-sided effects on tumour progression. m7G modulates therapeutic response, shaping chemosensitivity and resistance. m7G holds substantial clinical promise as a diagnostic/prognostic biomarker and a therapeutic target.

This study reveals that METTL1 and WDR4 are overexpressed in PCa and that, in DU145 cells, their knockdown was associated with suppressed m7G modification and attenuated oncogenic phenotypes. These model-specific findings suggest that METTL1/WDR4 may represent potential therapeutic targets in prostate cancer.

Furthermore, METTL1/WDR4-mediated m7G modification of SCLT1 regulates gefitinib resistance by activating the NF-κB signaling. Our findings reveal the crucial role of aberrant mRNA internal m7G modification in EGFR-TKIs resistance, suggesting that targeting the METTL1/WDR4-SCLT1-NF-κB axis holds a promising therapeutic potential for overcoming EGFR-TKIs resistance.

These novel insights indicate that m7G modification and its regulators hold significant potential for future clinical applications in the diagnosis and treatment of BC. In the future, how to apply m7G modifications to identify the implementation of clinically personalized BC treatment needs to be further explored.

These findings suggest that METTL1-WDR4 might serve as a potential diagnostic and prognostic biomarker and a therapeutic target for GC treatment by regulating m7G level.

In vivo, WDR4 knockdown inhibited tumor growth and metastasis while activating autophagy. In conclusion, the P300/ETV4-WDR4-m7G-SPP1 axis drives CRC progression by coupling epigenetic regulation, RNA modification, and autophagy inhibition, offering novel therapeutic targets.

Our study unveils the oncogenic roles of both METTL1 and WDR4 in prostate cancer development. Additionally, the prognostic model founded on METTL1 and WDR4 exhibits enhanced predictive precision for OS, thereby serving as a valuable clinical tool for prostate cancer.