线粒体RNA修饰（MRM）在调节关键线粒体基因的表达和促进肿瘤转移中发挥着至关重要的作用。尽管其意义重大，但低级别胶质瘤 (LGG) 中 MRM 的综合研究仍然未知。使用单细胞RNA-seq数据（GSE89567）评估LGG微环境中不同细胞类型中MRM相关基因的分布功能状态和相关性。我们基于 TCGA、CGGA、GSE16011 和 E-MTAB-3892 的多个批量 RNA-seq 数据集，通过使用 LASSO 回归分析和随机生存森林算法选择潜在的 MRM 相关基因，开发了 MRM 评分系统。对预后和免疫学特征、信号通路、代谢、体细胞突变和拷贝数变异（CNV）、治疗反应以及潜在小分子药物的预测进行了分析。从文献中总共筛选出35个MRM相关基因。对1120个正常脑组织和529个LGG的差异表达分析显示，分别有22个和10个基因上调和下调。大多数基因与 LGG 的预后相关。 METLL8、METLL2A、TRMT112 和 METTL2B 在所有细胞类型和每种细胞类型的不同细胞周期中广泛表达。几乎所有细胞类型都具有与线粒体 RNA 加工、核糖体生物发生或氧化磷酸化相关的簇。细胞间通讯和Pearson相关分析表明，MRM可能通过调节NCMA信号通路和ICP表达，促进有利于恶性进展的微环境的发展。通过LASSO和RSF算法分别观察到11个和9个MRM相关基因，最终利用6个MRM相关基因建立MRM评分系统（TRMT2B、TRMT11、METTL6、METTL8、TRMT6和TRUB2）。然后通过 qPCR 在神经胶质瘤和正常组织中验证这 6 个 MRM 相关基因。 MRM评分可以预测恶性临床特征、免疫浸润丰度、基因变异、临床结果、信号通路和代谢的富集程度。 体外实验表明，沉默 METTL8 可显着抑制神经胶质瘤细胞增殖并增强细胞凋亡。 MRM 评分高的患者对免疫疗法和小分子药物（如花生四烯基三氟甲基酮、MS.275、AH.6809、他克莫司和 TTNPB）表现出更好的反应。这些关于 MRM 在神经胶质瘤微环境中的生物学影响的新颖见解强调了其作为开发精确疗法（包括免疫治疗方法）的目标的潜力。© 2024。作者。

Mitochondrial RNA modification (MRM) plays a crucial role in regulating the expression of key mitochondrial genes and promoting tumor metastasis. Despite its significance, comprehensive studies on MRM in lower grade gliomas (LGGs) remain unknown. Single-cell RNA-seq data (GSE89567) was used to evaluate the distribution functional status, and correlation of MRM-related genes in different cell types of LGG microenvironment. We developed an MRM scoring system by selecting potential MRM-related genes using LASSO regression analysis and the Random Survival Forest algorithm, based on multiple bulk RNA-seq datasets from TCGA, CGGA, GSE16011, and E-MTAB-3892. Analysis was performed on prognostic and immunological features, signaling pathways, metabolism, somatic mutations and copy number variations (CNVs), treatment responses, and forecasting of potential small-molecule agents. A total of 35 MRM-related genes were selected from the literature. Differential expression analysis of 1120 normal brain tissues and 529 LGGs revealed that 22 and 10 genes were upregulated and downregulated, respectively. Most genes were associated with prognosis of LGG. METLL8, METLL2A, TRMT112, and METTL2B were extensively expressed in all cell types and different cell cycle of each cell type. Almost all cell types had clusters related to mitochondrial RNA processing, ribosome biogenesis, or oxidative phosphorylation. Cell-cell communication and Pearson correlation analyses indicated that MRM may promoting the development of microenvironment beneficial to malignant progression via modulating NCMA signaling pathway and ICP expression. A total of 11 and 9 MRM-related genes were observed by LASSO and the RSF algorithm, respectively, and finally 6 MRM-related genes were used to establish MRM scoring system (TRMT2B, TRMT11, METTL6, METTL8, TRMT6, and TRUB2). The six MRM-related genes were then validated by qPCR in glioma and normal tissues. MRM score can predict the malignant clinical characteristics, abundance of immune infiltration, gene variation, clinical outcome, the enrichment of signaling pathways and metabolism. In vitro experiments demonstrated that silencing METTL8 significantly curbs glioma cell proliferation and enhances apoptosis. Patients with a high MRM score showed a better response to immunotherapies and small-molecule agents such as arachidonyl trifluoromethyl ketone, MS.275, AH.6809, tacrolimus, and TTNPB. These novel insights into the biological impacts of MRM within the glioma microenvironment underscore its potential as a target for developing precise therapies, including immunotherapeutic approaches.© 2024. The Author(s).