对透明细胞肾细胞癌中 m6A 甲基组和转录组的综合分析。

Comprehensive analysis of m A methylome and transcriptome by Nanopore sequencing in clear cell renal carcinoma.

机构信息

Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Cancer Data Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Mol Carcinog. 2024 Apr;63(4):677-687. doi: 10.1002/mc.23680. Epub 2024 Feb 16.

Abstract

N -methyladenosine (m A) is the most prevalent epigenetic modification on eukaryotic messenger RNAs. Recent studies have focused on elucidating the key role of m A modification patterns in tumor progression. However, the relationship between m A and transcriptional regulation remains elusive. Nanopore technology enables the quantification of m A levels at each genomic site. In this study, a pair of tumor tissues and adjacent normal tissues from clear cell renal cell carcinoma (ccRCC) surgical samples were collected for Nanopore direct RNA sequencing. We identified 9644 genes displaying anomalous m A modifications, with 5343 genes upregulated and 4301 genes downregulated. Among these, 5224 genes were regarded as dysregulated genes, encompassing abnormal regulation of both m A modification and RNA expression. Gene Set Enrichment Analysis revealed an enrichment of these genes in pathways related to renal system progress and fatty acid metabolic progress. Furthermore, the χ test demonstrated a significant association between the levels of m A in dysregulated genes and their transcriptional expression levels. Additionally, we identified four obesity-associated genes (FTO, LEPR, ADIPOR2, and NPY5R) among the dysregulated genes. Further analyses using public databases revealed that these four genes were all related to the prognosis and diagnosis of ccRCC. This study introduced the novel approach of employing conjoint analysis of m A modification and RNA expression based on Nanopore sequencing to explore potential disease-related genes. Our work demonstrates the feasibility of the application of Nanopore sequencing technology in RNA epigenetic regulation research and identifies new potential therapeutic targets for ccRCC.

摘要

N6-甲基腺苷(m6A)是真核信使 RNA 上最普遍的表观遗传修饰。最近的研究集中在阐明 m6A 修饰模式在肿瘤进展中的关键作用。然而,m6A 与转录调控之间的关系仍不清楚。纳米孔技术能够在每个基因组位点定量 m6A 水平。在这项研究中,我们从透明细胞肾细胞癌(ccRCC)手术样本中收集了一对肿瘤组织和相邻的正常组织进行纳米孔直接 RNA 测序。我们鉴定了 9644 个显示异常 m6A 修饰的基因,其中 5343 个基因上调,4301 个基因下调。在这些基因中,有 5224 个被认为是失调基因,包括 m6A 修饰和 RNA 表达的异常调节。基因集富集分析显示,这些基因在与肾脏系统进展和脂肪酸代谢进展相关的途径中富集。此外,χ检验表明,失调基因中 m6A 水平与其转录表达水平之间存在显著关联。此外,我们在失调基因中鉴定出四个与肥胖相关的基因(FTO、LEPR、ADIPOR2 和 NPY5R)。使用公共数据库的进一步分析表明,这四个基因都与 ccRCC 的预后和诊断有关。本研究引入了一种新的方法,即基于纳米孔测序联合分析 m6A 修饰和 RNA 表达,以探索潜在的疾病相关基因。我们的工作证明了纳米孔测序技术在 RNA 表观遗传调控研究中的应用的可行性,并确定了 ccRCC 的新的潜在治疗靶点。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索