Department of Otolaryngology-Head and Neck Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
J Biochem Mol Toxicol. 2024 Jan;38(1):e23603. doi: 10.1002/jbt.23603. Epub 2023 Nov 28.
Head and neck squamous cell carcinoma (HNSC) is a common and fatal tumor with a bleak prognosis, posing a significant threat to human health. N6-methyladenosine (m6A) modification regulates tumor progression by modulating gene expression post-transcriptionally. Nevertheless, the specific function of m6A-modified tumor drivers in HNSC remains largely uncharted. In this study, we revealed the pro-oncogenic role of m6A-regulated NTMT1 in HNSC through comprehensive pan-cancer analysis and experimental validation. By scrutinizing the prognostic and expression profiles of NTMT1 across over 30 cancer types, we observed a significant association between NTMT1 and patient overall survival in ACC, HNSC, LAML, LGG, KIRC, and STAD. Moreover, we find a close correlation between NTMT1 and disease-free survival in ACC, HNSC, LUSC, UVM, KIRC, and STAD. NTMT1 exhibited dysregulation in 15 cancers, including CESC, CHOL, COAD, DLBC, GBM, HNSC, LGG, LIHC, PAAD, READ, SKCM, THYM, UCS, LAML, and TGCT. Integrated data underscored the critical involvement of NTMT1 in HNSC. Furthermore, the expression of NTMT1 was closely associated with tumor stage and immune infiltration in HNSC. Functionally, NTMT1 deficiency was demonstrated to significantly impede cell proliferation and cell-cycle progression in HNSC. Mechanistically, METTL3 was elucidated to mediate the epigenetic upregulation of NTMT1 in HNSC in an m6A-dependent manner, and the overexpression of METTL3 was shown to alleviate the inhibitory impact of downregulated NTMT1 on HNSC proliferation. In conclusion, our findings enhance our understanding of NTMT1's role across various cancer types and offer a rationale for clinically targeting NTMT1 as a therapeutic approach for HNSC.
头颈部鳞状细胞癌（HNSC）是一种常见且致命的肿瘤，预后不佳，对人类健康构成重大威胁。N6-甲基腺苷（m6A）修饰通过转录后调节基因表达来调节肿瘤进展。然而，m6A 修饰的肿瘤驱动因子在 HNSC 中的具体功能在很大程度上仍未被探索。在这项研究中，我们通过全面的泛癌症分析和实验验证，揭示了 m6A 调节的 NTMT1 在 HNSC 中的致癌作用。通过仔细研究 NTMT1 在超过 30 种癌症类型中的预后和表达谱，我们观察到 NTMT1 与 ACC、HNSC、LAML、LGG、KIRC 和 STAD 患者的总生存期之间存在显著关联。此外，我们发现 NTMT1 与 ACC、HNSC、LUSC、UVM、KIRC 和 STAD 中的无病生存期密切相关。NTMT1 在 15 种癌症中失调，包括 CESC、CHOL、COAD、DLBC、GBM、HNSC、LGG、LIHC、PAAD、READ、SKCM、THYM、UCS、LAML 和 TGCT。综合数据强调了 NTMT1 在 HNSC 中的关键作用。此外，NTMT1 的表达与 HNSC 中的肿瘤分期和免疫浸润密切相关。功能上，NTMT1 缺陷显著抑制 HNSC 中的细胞增殖和细胞周期进程。机制上，METTL3 介导了 m6A 依赖的 NTMT1 在 HNSC 中的表观遗传上调，并且 METTL3 的过表达减轻了下调的 NTMT1 对 HNSC 增殖的抑制作用。总之，我们的研究结果增强了我们对 NTMT1 在各种癌症类型中的作用的理解，并为将 NTMT1 作为治疗 HNSC 的一种治疗方法提供了依据。
