N1-甲基腺苷 (m1A) RNA 甲基化是一种新兴的表观遗传修饰。它在前列腺癌 (PCa) 的脂质代谢和预后中的潜在作用仍有待探索。本研究调查了 m1A 对脂质代谢和 PCa 预后的影响。在这项工作中，研究了 PCa 中 10 个广泛认可的 m1A 调节因子的遗传和表达变异情况被揭露了。结合机器学习策略，全面分析了癌症基因组图谱计划（TCGA）数据集中PCa样本的m1A修饰模式和相应的脂质代谢特征。我们进行了体外测定，以确定关键 m1A 调节因子 TRMT61A 对 PCa 细胞的作用。​​在 PCa 中发现了两种不同的 m1A 修饰模式和相应的脂质代谢谱。生化复发（BCR）高风险的m1A修饰亚群具有更强的线粒体代谢和FA氧化活性。构建了一致的 m1A 修饰相关脂质代谢评分（mMLMS）来预测 PCa 患者的 BCR 预后。 mMLMS 被证明可以准确预测 6 个外部队列中 PCa 的 BCR 预后。最后，TRMT61A被确定为与mMLMS相关的关键m1A调节因子，并被发现在体外促进PCa的进展。 TRMT61A 可能通过 PI3K/AKT 途径增强 PCa 细胞中的线粒体功能和 FA β 氧化。m1A RNA 甲基化模式与 PCa 的脂质代谢特征相关，从而提供一种新颖的治疗策略。版权所有 © 2024 Elsevier B.V。保留所有权利。

N1-methyladenosine (m1A) RNA methylation is an emerging epigenetic modification. Its potential role in lipid metabolism and prognosis of prostate cancer (PCa) remains unexplored.This study investigated the impact of m1A on lipid metabolism and PCa prognosis.In this work, the landscape of genetic and expression variations of 10 widely recognized m1A regulators in PCa was revealed. Combining machine-learning strategies, the m1A modification patterns and corresponding characteristics of lipid metabolism of PCa samples from the cancer genome atlas program (TCGA) dataset were comprehensively analyzed. In vitro assays were performed to identify the role of TRMT61A, the key m1A regulator, on PCa cells.Two distinct m1A modification patterns and corresponding lipid metabolism profiles were identified in PCa. The m1A modification subgroup with a high risk of biochemical recurrence (BCR) has stronger mitochondrial metabolism and FA oxidation activity. A consensus m1A modification-related lipid metabolism score (mMLMS) was constructed to predict the BCR prognosis of patients with PCa. The mMLMS was shown to accurately predict the BCR prognosis of PCa within six external cohorts. Finally, TRMT61A was identified as the key m1A regulator related to mMLMS, and it was found to promote the progression of PCa in vitro. TRMT61A potentially enhances mitochondrial function and FA beta oxidation in PCa cells via the PI3K/AKT pathway.m1A RNA methylation patterns are associated with characteristics of lipid metabolism in PCa, providing a novel treatment strategy.Copyright © 2024 Elsevier B.V. All rights reserved.