Abstract：
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.
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.
摘要：
背景：在全球范围内，鼻咽癌（NPC）是一种常见且致命的恶性肿瘤。尽管甲基转移酶如13（METTL13）的作用已在大多数人类癌症中得到强调，其在鼻咽癌中的作用和机制尚不清楚。
方法：使用定量实时PCR（qRT-PCR）检测NPC细胞系和正常细胞中METTL13的表达水平。进行了功能增益和损失实验。CCK-8,EdU,伤口愈合,Transwell和试管形成试验分别评估了增殖，迁徙,侵袭性和血管生成细胞反应。通过蛋白质印迹测量相应的蛋白质表达。染色质免疫沉淀（ChIP）测定用于验证ZEB1和TPT1启动子之间的关联。最终,为了证实METTL13在鼻咽癌中的关键作用，完成了体内肿瘤发生模型的建立。
结果：METTL13在NPC细胞中具有强化表达。METTL13沉默在体外显著抑制NPC细胞表型，包括增殖，迁徙,侵袭性和血管生成事件，以及阻碍体内肿瘤发生。此外,METTL13正调控ZEB1，而ZEB1可以与TPT1启动子结合并转录调控TPT1。还发现TPT1在NPC细胞中上调。TPT1沉默在体外抑制NPC细胞表型；TPT1过表达部分削弱了METTL13在NPC中的抗肿瘤作用。
结论：总之，METTL13上调ZEB1，促进TPT1的转录激活，最终促进NPC生长和转移，为NPC治疗提供潜在的治疗策略。
方法：使用定量实时PCR（qRT-PCR）检测NPC细胞系和正常细胞中METTL13的表达水平。进行了功能增益和损失实验。CCK-8,EdU,伤口愈合,Transwell和试管形成试验分别评估了增殖，迁徙,侵袭性和血管生成细胞反应。通过蛋白质印迹测量相应的蛋白质表达。染色质免疫沉淀（ChIP）测定用于验证ZEB1和TPT1启动子之间的关联。最终,为了证实METTL13在鼻咽癌中的关键作用，完成了体内肿瘤发生模型的建立。
结果：METTL13在NPC细胞中具有强化表达。METTL13沉默在体外显著抑制NPC细胞表型，包括增殖，迁徙,侵袭性和血管生成事件，以及阻碍体内肿瘤发生。此外,METTL13正调控ZEB1，而ZEB1可以与TPT1启动子结合并转录调控TPT1。还发现TPT1在NPC细胞中上调。TPT1沉默在体外抑制NPC细胞表型；TPT1过表达部分削弱了METTL13在NPC中的抗肿瘤作用。
结论：总之，METTL13上调ZEB1，促进TPT1的转录激活，最终促进NPC生长和转移，为NPC治疗提供潜在的治疗策略。
