PDF(Pubmed)
Abstract：
BACKGROUND: Lung cancer remains the foremost reason of cancer-related mortality, with invasion and metastasis profoundly influencing patient prognosis. N-acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)-acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non-small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC.
METHODS: We investigated NAT10\'s clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT-PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10\'s effects. A series of assays were carried out, including CCK-8, colony formation, wound healing, and transwell assays, to elucidate NAT10\'s role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient-derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings.
RESULTS: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E-cadherin level whereas decreased N-cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial-mesenchymal transition (EMT) pathway.
CONCLUSIONS: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.
METHODS: We investigated NAT10\'s clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT-PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10\'s effects. A series of assays were carried out, including CCK-8, colony formation, wound healing, and transwell assays, to elucidate NAT10\'s role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient-derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings.
RESULTS: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E-cadherin level whereas decreased N-cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial-mesenchymal transition (EMT) pathway.
CONCLUSIONS: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.
摘要：
背景：肺癌仍然是癌症相关死亡的首要原因，侵袭和转移对患者预后影响深远。N-乙酰转移酶10(NAT10)催化真核RNA中的专有N(4)-乙酰胞苷(ac4C)修饰。NAT10失调与各种疾病有关，然而，其在非小细胞肺癌（NSCLC）侵袭和转移中的作用尚不清楚。我们的研究探讨了NAT10在非小细胞肺癌中的临床意义和功能方面。
方法：我们使用癌症基因组图谱（TCGA）和一组98例NSCLC患者研究了NAT10的临床相关性。采用WB,qRT-PCR,和IHC分析，我们评估了NAT10在NSCLC组织中的表达，支气管上皮细胞（BECs），NSCLC细胞系,和小鼠异种移植物。Further,敲低和过表达技术(siRNA，shRNA,和质粒）用于评估NAT10的作用。进行了一系列的试验,包括CCK-8，集落形成，伤口愈合，和transwell分析，阐明NAT10在增殖中的作用，入侵,和转移。此外,我们利用肺癌患者来源的3D类器官，小鼠异种移植模型,和Remodelin（NAT10抑制剂）来证实这些发现。
结果：我们的研究显示NAT10在非小细胞肺癌组织中高表达，细胞系和小鼠异种移植模型。高NAT10水平与晚期T期相关，淋巴结转移和整体生存率差。NAT10击倒抑制了增殖，入侵,和移民,而NAT10过表达产生相反的效果。此外，NAT10水平降低与E-cadherin水平升高相关，而N-cadherin和波形蛋白表达降低，而升高的NAT10表达显示出对比结果。值得注意的是,重塑蛋白有效减弱NSCLC增殖，入侵,通过上皮-间质转化（EMT）途径抑制NAT10和迁移。
结论：我们的数据强调NAT10是NSCLC的潜在治疗靶点，提出了通过NAT10抑制靶向干预肺癌的途径。
方法：我们使用癌症基因组图谱（TCGA）和一组98例NSCLC患者研究了NAT10的临床相关性。采用WB,qRT-PCR,和IHC分析，我们评估了NAT10在NSCLC组织中的表达，支气管上皮细胞（BECs），NSCLC细胞系,和小鼠异种移植物。Further,敲低和过表达技术(siRNA，shRNA,和质粒）用于评估NAT10的作用。进行了一系列的试验,包括CCK-8，集落形成，伤口愈合，和transwell分析，阐明NAT10在增殖中的作用，入侵,和转移。此外,我们利用肺癌患者来源的3D类器官，小鼠异种移植模型,和Remodelin（NAT10抑制剂）来证实这些发现。
结果：我们的研究显示NAT10在非小细胞肺癌组织中高表达，细胞系和小鼠异种移植模型。高NAT10水平与晚期T期相关，淋巴结转移和整体生存率差。NAT10击倒抑制了增殖，入侵,和移民,而NAT10过表达产生相反的效果。此外，NAT10水平降低与E-cadherin水平升高相关，而N-cadherin和波形蛋白表达降低，而升高的NAT10表达显示出对比结果。值得注意的是,重塑蛋白有效减弱NSCLC增殖，入侵,通过上皮-间质转化（EMT）途径抑制NAT10和迁移。
结论：我们的数据强调NAT10是NSCLC的潜在治疗靶点，提出了通过NAT10抑制靶向干预肺癌的途径。
