The rapid advances in epigenetic and epitranscriptomic regulatory mechanisms have opened new prospects for precision therapies in various diseases. N-acetyltransferase 10 (NAT10) is currently the only known eukaryotic RNA ac4C acetyltransferase and has also been reported to acetylate multiple protein substrates, regulating diverse physiological processes. In this review, we comprehensively describe the domain organization, structural features and subcellular localization of NAT10. The molecular mechanisms underlying NAT10-mediated RNA ac4C modification and protein acetylation, as well as their biological functions across physiological and pathological contexts, are systematically summarized, with the aim of facilitating its clinical translation. Furthermore, we review the recent advances in NAT10-targeted therapeutic strategies, discuss the potential for combining NAT10-targeted strategies with existing treatment modalities, and propose possible approaches for optimization. By integrating current evidence, this review provides insights into the functions of NAT10 and highlights future research directions for its validation and translational development as a clinical therapeutic target in various diseases.
Chengyu Zhang, Jin Lu, Lu Tang et al.· Cell Biology and Toxicology· 0 citations
Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) has been implicated in tumor suppression, but its role in breast cancer remains unclear. This study evaluated the expression pattern, prognostic value, immune infiltration association, methylation status, and biological function of TP53AIP1 in breast cancer using TCGA transcriptomic data, public methylation datasets, immunohistochemistry, and in vitro experiments. TP53AIP1 was significantly downregulated in breast cancer tissues and was identified as an independent prognostic factor for poor survival. TP53AIP1 expression was positively associated with transcriptome-estimated infiltration of natural killer cells, mast cells, and plasmacytoid dendritic cells. Methylation analysis showed that TP53AIP1 promoter hypermethylation was associated with reduced TP53AIP1 expression, suggesting a potential epigenetic silencing mechanism. Functionally, TP53AIP1 overexpression suppressed breast cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition and, promoted apoptosis and cell-cycle arrest. Mechanistically, TP53AIP1 overexpression reduced MEK/ERK phosphorylation, whereas MAPK pathway reactivation partially reversed its inhibitory effects on malignant phenotypes. These findings suggest that TP53AIP1 may serve as a potential prognostic biomarker and tumor-suppressive candidate in breast cancer, with its effects at least partly associated with MAPK pathway attenuation.
Meihai Deng, Xueting Wu, J. Bai et al.· Discover Oncology· 0 citations