WTAP (WT1 Associated Protein)

WTAP stabilized MMP12 expression via m6A modification, thereby enhancing the malignant phenotypes of EC cells. Clinically, targeting the WTAP-MMP12 axis could represent a promising therapeutic strategy to inhibit EC progression.

In the HTVi HCC model, the combination of WTAP knockdown with sorafenib markedly suppressed tumor progression and boosted survival rates. These findings highlight that WTAP positively regulates the ERK pathway in HCC, promoting sorafenib resistance; therefore, targeting WTAP may represent a novel strategy to potentiate sorafenib responsiveness in HCC.

In this study, we elucidate a novel positive feedback loop in GBM where IGF2BP3 stabilizes m6A-modified GP130 mRNA, activating the JAK2/STAT3 pathway, which subsequently transcriptionally upregulates WTAP, thereby synergistically enhancing m6A modification and tumorigenesis.

WTAP epitranscriptomically regulates VSMC ferroptosis via the GAS5/EZH2/IRF4/FTH1 axis, revealing a novel mechanism in vascular restenosis pathogenesis and a potential therapeutic target. Antioxid. Redox Signal. 00, 000-000.

These findings elucidate a molecular pathway through which NGR1, via ABCG2 mediated transport, mitigates UVB induced DNA damage responses by promoting m6A dependent DNA repair, positioning it as a promising candidate for topical therapeutic intervention. SIGNIFICANCE STATEMENT: Mechanisms by which NGR1 alleviates UVB induced skin sunburn injury via the WTAP/m6A axis and ABCG2 mediated trafficking offer a promising avenue for developing improved epidermal therapeutics for the related skin disorders.

miR-425-5p is lowly expressed in the group of moderate to severe neonatal brain injury and may participate in the inflammatory response of brain injury through WTAP.

Here, we investigated m6A-RNA spatial and quantitative abundance and expression of m6A effector proteins directly in GBM tissue and patient-derived low-passage primary adult GBM and low-grade glioma (LGG) cells, and explored the consequences of m6A-RNA disruption on GBM invasive capabilities, self-renewal and responsiveness to temozolomide (TMZ)...Functional depletion of these effector proteins significantly altered m6A levels on and the expression of the pluripotency stem cell marker SOX2 while also impairing self-renewal and cell invasion behaviour and increasing sensitivity to TMZ. The targeting of RNA modification regulatory mechanisms reveals novel therapeutic strategies aimed at improving clinical outcomes for GBM patients.

In addition, the levels of WTAP pS176 and GAC expression, which were mutually correlated, were positively associated with poor prognosis of patients with HCC. These findings uncover a critical mechanism by which tumor cells counteract ferroptosis by WTAP-mediated GLS alternative splicing under EGFR activation, highlighting the therapeutic potential of targeting the m6A-dependent GLS isoform switch in HCC and offering a rationale for the development of combination therapies.

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.