N1-甲基拉第义胺RNA甲基化模式与前列腺癌生化复发的风险增加有关，并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
影响因子:4.70000
分区:医学2区 / 药学2区 免疫学3区
发表日期:2024 Dec 25
作者:
Yulin Deng, Zeheng Tan, Shanghua Cai, Yuanfa Feng, Zhenfeng Tang, Jinchuang Li, Huichan He, Zhenjie Wu, Ren Liu, Huiting Huang, Jianheng Ye, Zhaodong Han, Weide Zhong
摘要
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）（PCA）中的潜在作用尚未探索。这项研究研究了M1A对脂质代谢和PCA预后的影响。在这项工作中，PCA中有10种遗传和表达变化的遗传和表达变化的景观。全面分析了机器学习策略，M1A修饰模式和PCA样品中PCA样品脂质代谢的相应特征。进行了体外测定，以确定关键M1A调节剂TRMT61A在PCA细胞上的作用。两种不同的M1A修饰模式，并在PCA中鉴定了相应的脂质代谢谱。具有高生化复发风险（BCR）的M1A修饰亚组具有更强的线粒体代谢和FA氧化活性。构建了共识M1A修饰相关的脂质代谢评分（MMLMS），以预测PCA患者的BCR预后。显示MMLM可准确预测六个外部队列中PCA的BCR预后。最后，将TRMT61A鉴定为与MMLM有关的关键M1A调节剂，并发现它在体外促进PCA的进展。 TRMT61A可能通过PI3K/AKT途径在PCA细胞中增强线粒体功能和FAβ氧化。M1ARNA RNA甲基化模式与PCA中脂质代谢的特征有关，提供了一种新的治疗策略。
Abstract
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.