College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang Province 150081, China.
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, Hainan Province 571199, China.
Biomed Res Int. 2020 Mar 20;2020:8595473. doi: 10.1155/2020/8595473. eCollection 2020.
Noncoding RNAs (ncRNAs), especially microRNA (miRNA) and long noncoding RNA (lncRNA), have an impact on a variety of important biological processes during colon adenocarcinoma (COAD) progression. This includes chromatin organization, transcriptional and posttranscriptional regulation, and cell-cell signaling. The aim of this study is to identify the ncRNA-regulated modules that accompany the progression of COAD and to analyze their mechanisms, in order to screen the potential prognostic biomarkers for COAD. An integrative molecular analysis was carried out to identify the crosstalks of gene modules between different COAD stages, as well as the essential ncRNAs in the posttranscriptional regulation of these modules. 31 ncRNA regulatory modules were found to be significantly associated with overall survival in COAD patients. 17 out of the 31 modules (in which ncRNAs played essential roles) had improved the predictive ability for COAD patient survival compared to only the mRNAs of those modules, which were enriched in the core cancer hallmark pathways with closer interactions. These suggest that the ncRNAs' regulatory modules not only exhibit close relation to COAD progression but also reflect the dynamic significant crosstalk of genes in the modules to the different malignant extent of COAD.
非编码 RNA(ncRNAs),特别是 microRNA(miRNA)和长非编码 RNA(lncRNA),在结肠腺癌(COAD)进展过程中对多种重要的生物学过程有影响。这包括染色质组织、转录和转录后调控以及细胞间信号传递。本研究的目的是鉴定伴随 COAD 进展的 ncRNA 调控模块,并分析其机制,以筛选 COAD 的潜在预后生物标志物。进行了综合分子分析,以鉴定不同 COAD 阶段之间基因模块之间的串扰,以及这些模块中转录后调控的必需 ncRNAs。发现 31 个 ncRNA 调控模块与 COAD 患者的总生存率显著相关。在 31 个模块中有 17 个(其中 ncRNAs 起关键作用)与仅包含这些模块的 mRNAs 相比,改善了对 COAD 患者生存的预测能力,这些模块在核心癌症特征途径中富集,并且相互作用更密切。这表明 ncRNAs 的调控模块不仅与 COAD 的进展密切相关,而且反映了模块中基因的动态显著串扰与 COAD 的不同恶性程度有关。