Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
Donald Bren School of Information and Computer Sciences, University of California, Irvine, USA.
Med Oncol. 2022 Jul 14;39(10):140. doi: 10.1007/s12032-022-01736-6.
N-acetyltransferase 10 (NAT10) is a nucleolar acetyltransferase and has been reported to facilitate tumorigenesis in various cancers, but its role in NSCLC and how it is regulated remain to be assessed. The expression of NAT10 was explored in online databases and our collected clinical specimens. The relationship of NAT10 and clinical characteristics was evaluated using the online databases. Functional analyses were utilized to determine the effect of NAT10 on the proliferation and migration abilities. KEGG pathway analyses were conducted to investigate NAT10-related pathways in NSCLC. The influence of NAT10 on cell cycle was assessed by flow cytometry and cell synchronization assay. The association between c-myc and NAT10 promoter was determined by ChIP. Compared with normal tissue, NAT10 was significantly overexpressed in NSCLC. Upregulated NAT10 was associated with more advanced stage for lung adenocarcinoma and shorter overall survival and first progression time for lung cancer. NAT10 could promote proliferation and migration of NSCLC cells in vitro. c-myc positively regulated the expression of NAT10 as a transcription factor. KEGG pathway analyses indicated that NAT10 was significantly involved in cell cycle regulation, cytokine-cytokine receptor interaction and other pathways. The knockdown of NAT10-induced G1 arrest, which was possibly mediated by the downregulation of cyclin D1.Our findings suggested that c-myc-mediated upregulation of NAT10 promoted the proliferation and migration of NSCLC cells and NAT10 might be a marker for prognosis and a promising target for treatment in NSCLC.
N-乙酰基转移酶 10（NAT10）是一种核仁乙酰转移酶，已被报道在各种癌症中促进肿瘤发生，但它在非小细胞肺癌中的作用及其调节方式仍有待评估。本研究在在线数据库和我们收集的临床标本中探索了 NAT10 的表达情况。利用在线数据库评估了 NAT10 与临床特征的关系。通过功能分析来确定 NAT10 对增殖和迁移能力的影响。通过 KEGG 通路分析研究了 NSCLC 中与 NAT10 相关的通路。通过流式细胞术和细胞同步化实验评估了 NAT10 对细胞周期的影响。通过 ChIP 确定 c-myc 与 NAT10 启动子之间的关联。与正常组织相比，NAT10 在非小细胞肺癌中显著过表达。上调的 NAT10 与肺腺癌的更晚期阶段以及肺癌患者的总生存期和首次进展时间更短相关。NAT10 可以促进非小细胞肺癌细胞在体外的增殖和迁移。c-myc 作为转录因子正向调节 NAT10 的表达。KEGG 通路分析表明，NAT10 显著参与细胞周期调控、细胞因子-细胞因子受体相互作用等通路。NAT10 的敲低诱导 G1 期阻滞，这可能是通过下调细胞周期蛋白 D1 介导的。我们的研究结果表明，c-myc 介导的 NAT10 上调促进了非小细胞肺癌细胞的增殖和迁移，NAT10 可能是非小细胞肺癌的预后标志物和有前途的治疗靶点。
