Department of Otolaryngology Head and Neck surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China.
Department of Otolaryngology Head and Neck surgery, Jiange People's Hospital, Jiange, Sichuan, China.
J Gene Med. 2023 May;25(5):e3476. doi: 10.1002/jgm.3476. Epub 2023 Mar 22.
Globally, nasopharyngeal carcinoma (NPC) is a prevalent and deadly malignancy. Despite the role of methyltransferase like 13 (METTL13) having been highlighted in a majority of human cancers, its function and mechanism in NPC is indistinct.
The expression level of METTL13 in NPC cell lines and normal cells was detected using a quantitative real-time polymerase chain reaction. Gain- and loss-of function experiments were conducted. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound-healing, Transwell and tube formation assays, respectively, appraised the proliferative, migratory, invasive and angiogenic cellular responses. Corresponding protein expression was measured by western blotting. A chromatin immunoprecipitation assay was applied to verify the association between ZEB1 and the TPT1 promoter. Eventually, to substantiate the critical role of METTL13 in NPC, the establishment of an in vivo tumorigenesis model was accomplished.
METTL13 possessed fortified expression in NPC cells. METTL13 silencing markedly suppressed NPC cellular phenotypes in vitro, including proliferative, migratory, invasive and angiogenic events, as well as hindered tumorigenesis in vivo. Additionally, METTL13 positively regulated ZEB1, whereas ZEB1 could bind to TPT1 promoter and transcriptionally regulate TPT1. TPT1 was also found to be upregulated in NPC cells. TPT1 silencing suppressed NPC cellular phenotypes in vitro. TPT1 overexpression partly weakened the anti-tumor effect of METTL13 in NPC.
In summary, METTL13 up-regulated ZEB1, which facilitated the transcriptional activation of TPT1, ultimately promoting NPC growth and metastasis, providing a potential therapeutic strategy for NPC treatment.
在全球范围内，鼻咽癌（NPC）是一种常见且致命的恶性肿瘤。尽管甲基转移酶样 13（METTL13）在大多数人类癌症中都具有重要作用，但它在 NPC 中的功能和机制尚不清楚。
通过实时定量聚合酶链反应检测 NPC 细胞系和正常细胞中 METTL13 的表达水平。进行增益和缺失功能实验。细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷、划痕愈合、Transwell 和管形成测定分别评估细胞的增殖、迁移、侵袭和血管生成反应。通过蛋白质印迹法测量相应的蛋白表达。应用染色质免疫沉淀测定来验证 ZEB1 与 TPT1 启动子之间的关联。最终，通过建立体内肿瘤发生模型来证实 METTL13 在 NPC 中的关键作用。
METTL13 在 NPC 细胞中表达增强。METTL13 沉默显著抑制 NPC 细胞的体外表型，包括增殖、迁移、侵袭和血管生成事件，并抑制体内肿瘤发生。此外，METTL13 正向调节 ZEB1，而 ZEB1 可以结合到 TPT1 启动子并转录调节 TPT1。还发现 TPT1 在 NPC 细胞中上调。TPT1 沉默抑制 NPC 细胞的体外表型。TPT1 过表达部分削弱了 METTL13 在 NPC 中的抗肿瘤作用。
综上所述，METTL13 上调 ZEB1，促进 TPT1 的转录激活，最终促进 NPC 的生长和转移，为 NPC 的治疗提供了一种潜在的治疗策略。
