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

• Published in: Cell reports (Cambridge) Vol. 42; no. 3; p. 112261
• Main Authors: Shen, Sipeng, Chen, Jiajin, Li, Hongru, Jiang, Yunke, Wei, Yongyue, Zhang, Ruyang, Zhao, Yang, Chen, Feng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.03.2023; Elsevier
• Subjects: CP: Cancer; DNA methylation; DNA Methylation - genetics; Humans; MicroRNAs; multi-omics; Neoplasms - genetics; non-coding RNA; overall survival; pan-cancer; Proteomics; RNA, Long Noncoding - genetics; RNA, Small Nucleolar; RNA, Untranslated - genetics; Tumor Microenvironment; DNA methylation; overall survival; multi-omics; pan-cancer; non-coding RNA; CP: Cancer
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112261

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/). [Display omitted] •We describe the non-coding RNA quantitative trait methylation sites across 32 cancer types•Most DNAm sites are in trans association rather than cis association•The ncQTM-derived ncmcluster is associated with clinical outcome•This study provides an online database to systematically describe the ncQTM patterns Characterizing influences of DNA methylation on non-coding RNAs is important to understand the mechanisms of gene regulation. By performing pan-cancer association analyses, Shen et al. comprehensively describe the associations between non-coding RNAs and DNA methylation features in a large-scale population. An online database is developed to systematically describe their patterns.