RNA 中异常的 N6-甲基腺苷 (m6A) 甲基化通过影响 mRNA 代谢、选择性剪接、易位、稳定性和翻译，在多种肿瘤的发病机制中发挥着关键作用。然而，m6A 修饰在肺腺癌进展中的具体调节因子和潜在机制尚不清楚。在这项研究中，我们分析了从癌症基因组图谱 (TCGA) 数据库下载的 RNA-seq 转录组数据，发现“m6A writer”RNA 结合基序蛋白 15 (RBM15) 表达在肺腺癌 (LUAD) 活检中显着升高，并且较高的 RBM15 水平与 LUAD 患者较差的总生存期 (OS) 相关。进一步的研究证实 RBM15 在 LUAD 组织和细胞系中显着表达。此外，在PC9和H1299细胞中沉默RBM15可减少体外和体内的细胞增殖，而在A549细胞中过度表达RBM15则促进细胞生长。从机制上讲，乳酸脱氢酶 A (LDHA) 是 RBM15 的下游靶标。 RBM15 介导的 LDHA mRNA 的 m6A 修饰增强了其稳定性，从而在 LUAD 中发挥致癌作用。总而言之，我们的研究结果表明 RBM15/LDHA 轴可能是 LUAD 的一个新颖且有前途的治疗靶点。版权所有 © 2024。由 Elsevier Inc. 出版。

Abnormal N6-methyladenosine (m6A) methylation in RNA plays a pivotal role in the pathogenesis of many types of tumors by influencing mRNA metabolism, alternative splicing, translocation, stability and translation. However, the specific regulators and underlying mechanisms of m6A modification in the progression of lung adenocarcinoma are not well understood. In this study, we analyzed the RNA-seq transcriptome data downloaded from The Cancer Genome Atlas (TCGA) database, and identified "m6A writer" RNA binding motif protein 15 (RBM15) expression was significantly elevated in lung adenocarcinoma (LUAD) biopsies, and the higher RBM15 levels were correlated with the poorer overall survival (OS) of LUAD patients. Further study confirmed RBM15 was prominently expressed in LUAD tissues and cell lines. Moreover, silencing RBM15 in PC9 and H1299 cells reduced cell proliferation both in vitro and in vivo, while overexpression of RBM15 in A549 cells promoted cell growth. Mechanistically, lactate dehydrogenase A (LDHA) acted as a downstream target of RBM15. RBM15-mediated m6A modification of LDHA mRNA enhanced its stability to exert an oncogenic role in LUAD. Taken together, our findings suggest that the RBM15/LDHA axis might be a novel and promising therapeutic target for LUAD.Copyright © 2024. Published by Elsevier Inc.