长非编码 RNA (lncRNA) 的失调以多种方式参与调节肿瘤进展。然而，人们对lncRNA是否参与蛋白质翻译调控知之甚少。在这里，我们通过分析 lncRNA 微阵列，发现炎症巨噬细胞凋亡抑制因子 lncRNA (SIMALR) 在鼻咽癌 (NPC) 组织中高表达。临床上，SIMALR的高表达可作为鼻咽癌患者预后不良的独立预测因子。 SIMALR 作为致癌 lncRNA 发挥作用，在体外和体内促进鼻咽癌细胞的增殖和转移。从机制上讲，SIMALR 通过与 eEF1A2（真核翻译延伸因子 1 α 2）（真核细胞翻译机制中最重要的调节因子之一）结合，并增强其内源性 GTP 酶活性，成为蛋白质合成的关键加速器。此外，SIMALR介导eEF1A2磷酸化的激活，加速ITGB4/ITGA6的翻译，最终促进鼻咽癌细胞的恶性表型。此外，N-乙酰转移酶 10 (NAT10) 增强了 SIMALR 的稳定性，并通过 N4-乙酰胞苷 (ac4C) 修饰导致其在 NPC 中过度表达。总之，我们的结果说明了 SIMALR 作为蛋白质翻译加速器的功能，并强调了 NAT10-SIMALR-eEF1A2-ITGB4/6 轴在 NPC 中的致癌作用。© 2024。作者，获得 Springer Nature Limited 的独家许可。

The dysregulation of long non-coding RNAs (lncRNAs) are involved in regulating tumor progression in multiple manner. However, little is known about whether lncRNA is involved in the translation regulation of proteins. Here, we identified that the suppressor of inflammatory macrophage apoptosis lncRNA (SIMALR) was highly expressed in nasopharyngeal carcinoma (NPC) tissues by analyzing the lncRNA microarray. Clinically, the high expression of SIMALR served as an independent predictor for inferior prognosis in NPC patients. SIMALR functioned as an oncogenic lncRNA that promoted the proliferation and metastasis of NPC cells in vitro and in vivo. Mechanistically, SIMALR served as a critical accelerator of protein synthesis by binding to eEF1A2 (eukaryotic translation elongation factor 1 alpha 2), one of the most crucial regulators in the translation machinery of the eukaryotic cells, and enhancing its endogenous GTPase activity. Furthermore, SIMALR mediated the activation of eEF1A2 phosphorylation to accelerate the translation of ITGB4/ITGA6, ultimately promoting the malignant phenotype of NPC cells. In addition, N-acetyltransferase 10 (NAT10) enhanced the stability of SIMALR and caused its overexpression in NPC through the N4-acetylcytidine (ac4C) modification. In sum, our results illustrate SIMALR functions as an accelerator for protein translation and highlight the oncogenic role of NAT10-SIMALR-eEF1A2-ITGB4/6 axis in NPC.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.