研究动态
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人类癌症中非编码RNA与DNA甲基化的大规模整合。

Large-scale integration of the non-coding RNAs with DNA methylation in human cancers.

发表日期:2023 Mar 15
作者: Sipeng Shen, Jiajin Chen, Hongru Li, Yunke Jiang, Yongyue Wei, Ruyang Zhang, Yang Zhao, Feng Chen
来源: MEDICINE & SCIENCE IN SPORTS & EXERCISE

摘要:

描述DNA甲基化(DNAm)对非编码RNA(ncRNA)影响的特征对于理解基因调控和癌症预后的机制至关重要。在我们的研究中,我们描述了对来自癌症基因组图谱(TCGA)8,545个样本、临床蛋白质瘤分析联盟(CPTAC)763个样本和基因型-组织表达(GTEx)516个样本的ncRNA定量性状甲基化位点(ncQTM)分析结果,以确认DNAm位点和ncRNA(miRNA、长非编码RNA [lncRNA]、小核RNA [snRNA]、小核仁RNA [snoRNA]和rRNA)之间的显著关联,跨过32种癌症类型。在超过220亿次测试中,我们发现302,764个cis-ncQTMs(所有测试的6.28%)和79,841,728个trans-ncQTMs(所有测试的1.15%)。大多数DNAm位点(平均70.6%)是在转录联合作用中,而只有25.2%的DNAm位点是在顺式作用中。此外,我们基于特异性癌症ncRNAs开发了一种名为ncmcluster的亚型,该亚型与肿瘤微环境、临床结果和生物通路有关。为了全面描述ncQTM模式,我们开发了一个名为Pancan-ncQTM(http://bigdata.njmu.edu.cn/Pancan-ncQTM/)的数据库。版权所有©2023作者。由Elsevier Inc.出版,保留所有权利。
Characterizing influences of DNA methylation (DNAm) on non-coding RNAs (ncRNAs) is important to understand the mechanisms of gene regulation and cancer outcome. In our study, we describe the results of ncRNA quantitative trait methylation sites (ncQTM) analyses on 8,545 samples from The Cancer Genome Atlas (TCGA), 763 samples from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and 516 samples from Genotype-Tissue Expression (GTEx) to identify the significant associations between DNAm sites and ncRNAs (miRNA, long non-coding RNA [lncRNA], small nuclear RNA [snRNA], small nucleolar RNA [snoRNA], and rRNA) across 32 cancer types. With more than 22 billion tests, we identify 302,764 cis-ncQTMs (6.28% of all tested) and 79,841,728 trans-ncQTMs (1.15% of all tested). Most DNAm sites (70.6% on average) are in trans association, while only 25.2% DNAm sites are in cis association. Further, we develop a subtype named ncmcluster based on cancer-specific ncRNAs thatis associated with tumor microenvironment, clinical outcome, and biological pathways. To comprehensively describe the ncQTM patterns, we developed a database named Pancan-ncQTM (http://bigdata.njmu.edu.cn/Pancan-ncQTM/).Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.