WTAP (WT1 Associated Protein)

Ciapin1 knockdown exacerbated renal tissue injury, apoptosis, mitochondrial damage, and inflammation in a murine AKI model induced by cecal ligation and puncture. This study uncovers the CIAPIN1-OPA1 signaling axis as a novel mechanistic basis for SA-AKI, wherein it regulates mitochondrial function, inflammatory response, and cellular apoptosis in renal tissues under septic stress.

Moreover, overexpression of GCH1 reversed Cur-induced ferroptosis and malignant phenotype inhibition in A549 and H520 NSCLC cells. Our study suggested that Cur induced ferroptosis and suppressed malignant phenotypes in NSCLC in part through the WTAP-GCH1 axis, thereby revealing a novel mechanism for its therapeutic potential.

Understanding these mechanisms offers opportunities for exploiting WTAP as a biomarker and therapeutic target across multiple cancer types. This review explores the multifaceted role of WTAP in cancer, focusing on its mechanisms of action in tumorigenesis, immune modulation, and therapy resistance, and offers insights into potential therapeutic strategies targeting WTAP in cancer treatment.

The WTAP/TP53BP1 axis impairs periodontal tissue regeneration by promoting P-PDLSC senescence and suppressing osteogenic differentiation in an m6A-dependent manner, revealing a new cellular-level target for treating periodontitis.

Art emerges as a clinically potential HCC therapeutic that elicits its oncosuppressive activity through WTAP/YTHDC2-mediated m6A methylation of ATG5 transcripts, thereby causes ferroptosis of HCC mediated by autophagy.

We developed a novel predictive panel of serum m6A-related genes that could empower CRC screening and early diagnosis. METTL14, ALKBH5, YTHDC2 expression, and SOX2 protein correlate with tumor-related data and are candidates for CRC prognosis.

Together, the evidence supports the SAM-m6A axis as a practical framework to connect nutrient state with RNA fate decisions. It also highlights key gaps for translation, including target engagement, dose-exposure alignment, and causal validation of m6A-dependent phenotypes.

Moreover, we demonstrated that the high-risk factor AC129507.1 in the lncRNA signature was a novel target of the m6A regulatory axis WTAP/YTHDF3/ALKBH5, and depletion of AC129507.1 could markedly induce ferroptosis in GC. Collectively, these findings provide a candidate strategy for risk classification and better clinical management of GC and shed new insight into the underlying mechanism of AC129507.1 in GC development.

Therapeutically, targeting ROR1 via endothelial-specific Adno-Associated Virus (AAV) knockdown or the antibody-drug conjugate Zilovertamab vedotin (VLS-101) normalizes vasculature, improves temozolomide delivery, and sensitizes tumors in glioblastoma organoids and xenografts. These findings highlight the ROR1-WNT5A axis as a promising target in glioblastomas treatment.

WTAP stimulated tumor growth in vivo and suppressed ferroptosis by stabilizing SF3B1 expression. In conclusion, WTAP effectively suppressed ferroptosis in EC cells by modulating SF3B1 via m6A methylation, thereby aggravating EC.

Due to their diagnostic, prognostic and predictive value, m6A regulators have emerged as promising biomarkers in gynaecological cancers in recent years. This review highlights the role of m6A regulators and critically evaluates their biomarker and clinical potential in gynaecological cancers.