N1-甲基腺苷 RNA 甲基化模式与前列腺癌生化复发风险增加相关，并可作为患者分层的潜在新型生物标志物。

N1-methyladenosine RNA methylation patterns are associated with an increased risk to biochemical recurrence in prostate cancer and serve as a potential novel biomarker for patient stratification.

机构信息

Guangdong Provincial Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 510120, Guangzhou, Guangdong, China; Guangzhou National Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, 510005, Guangzhou, Guangdong, China.

Department of Urology, Zhujiang Hospital, Southern Medical University, 510260, Guangzhou, Guangdong, China.

出版信息

Int Immunopharmacol. 2024 Dec 25;143(Pt 2):113404. doi: 10.1016/j.intimp.2024.113404. Epub 2024 Oct 20.

DOI:10.1016/j.intimp.2024.113404

PMID:39433012

Abstract

INTRODUCTION

N1-methyladenosine (m1A) RNA methylation is an emerging epigenetic modification. Its potential role in lipid metabolism and prognosis of prostate cancer (PCa) remains unexplored.

OBJECTIVES

This study investigated the impact of m1A on lipid metabolism and PCa prognosis.

METHODS

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.

RESULTS

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.

CONCLUSION

m1A RNA methylation patterns are associated with characteristics of lipid metabolism in PCa, providing a novel treatment strategy.

摘要

简介

N1-甲基腺苷（m1A）RNA 甲基化是一种新兴的表观遗传修饰。其在前列腺癌（PCa）中的脂质代谢和预后中的潜在作用尚未可知。

目的

本研究探讨了 m1A 对脂质代谢和 PCa 预后的影响。

方法

在这项工作中，揭示了 10 种广泛认可的 m1A 调节因子在 PCa 中的遗传和表达变化的全景。结合机器学习策略，全面分析了来自癌症基因组图谱计划（TCGA）数据集的 PCa 样本中 m1A 修饰模式及其对应的脂质代谢特征。进行了体外实验以鉴定关键的 m1A 调节因子 TRMT61A 在 PCa 细胞中的作用。

结果

鉴定出 PCa 中存在两种不同的 m1A 修饰模式和对应的脂质代谢特征。具有高生化复发（BCR）风险的 m1A 修饰亚组具有更强的线粒体代谢和 FA 氧化活性。构建了一个共识的 m1A 修饰相关的脂质代谢评分（mMLMS），用于预测 PCa 患者的 BCR 预后。mMLMS 被证明可以准确预测六个外部队列中 PCa 的 BCR 预后。最后，鉴定出 TRMT61A 是与 mMLMS 相关的关键 m1A 调节因子，并且发现它在体外促进了 PCa 的进展。TRMT61A 通过 PI3K/AKT 通路潜在增强了 PCa 细胞中线粒体功能和 FAβ氧化。