Department of Gastroenterology, The Second Hospital of Anhui Medical University, Hefei, China.
School of Public Health of Anhui Medical University, Hefei, China.
Ann Palliat Med. 2021 Sep;10(9):9627-9639. doi: 10.21037/apm-21-1952.
Crohn's disease (CD) is a chronic inflammatory disease of the digestive tract. The underlying molecular mechanism of CD remains unclear. The aim of this study was to investigate the differentially expressed long non-coding RNA (lncRNA) in CD and its possible mechanism, and to verify the expression of lncRNA.
Microarray GSE67106 and GSE83448 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed lncRNAs (DELs) and messenger RNAs (mRNAs, DEGs), when normalized through the betaqn package in the R, were determined via the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG) pathways were studied using the database for the annotation, visualization and integrated discovery (DAVID) version 6.7, along with Gene Set Enrichment Analysis (GSEA) version 3.0. The co-expression of lncRNAs-mRNAs were determined using weighted gene co expression network analysis (WGCNA). The micro RNAs (miRNAs) related to the DELs and DEGs were forecast. A competing endogenous RNA (ceRNA) network was established.
There were 42 DEGs and 551 DEGs identified in total among the samples of the CD and normal control, respectively. These DEGs were enriched in such pathways as retinol metabolism, renin angiotensin system, and maturation-related signaling pathways. A lncRNA-mRNA co-expression network was constructed by WGCNA, with CDKN2B-AS (ANRIL), CTC-210G5.1.1, RP11-467L20.10.1, RP11-325F22.5.1, and RP11-59E19.1.1 as hub DELs. Together with miRNAs, a ceRNA network was constructed and functional analysis showed that the cell brush border and plasma membrane, synthesis and transport of lipoprotein, and angiotensin maturation, metabolism, and regulation of blood pressure were involved in the progression of CD. We successfully validated 1 lncRNA ANRIL, in our clinical specimens, ANRIL, which can feature prominently in CD. However, the exact mechanism of lncRNA ANRIL in CD prediction and diagnosis requires further exploration.
This study showed that lncRNA ANRIL has a certain predictive effect on CD occurrence and development and could be a new potential treatment target.
克罗恩病（CD）是一种慢性消化道炎症性疾病。CD 的潜在分子机制尚不清楚。本研究旨在探讨 CD 中差异表达的长非编码 RNA（lncRNA）及其可能的机制，并验证 lncRNA 的表达。
从基因表达综合数据库（GEO）中下载微阵列 GSE67106 和 GSE83448。通过 R 中的 betaqn 包对数据进行标准化后，使用 limma 包确定差异表达的 lncRNA（DELs）和信使 RNA（mRNAs，DEGs）。使用数据库注释、可视化和综合发现（DAVID）版本 6.7 以及基因集富集分析（GSEA）版本 3.0 研究基因本体论（GO）和京都基因与基因组百科全书（KEGG）途径。通过加权基因共表达网络分析（WGCNA）确定 lncRNA-mRNA 的共表达。预测与 DELs 和 DEGs 相关的 microRNAs（miRNAs）。建立竞争内源性 RNA（ceRNA）网络。
在 CD 和正常对照的样本中，共鉴定出 42 个 DEGs 和 551 个 DEGs。这些 DEGs 富集在视黄醇代谢、肾素-血管紧张素系统和成熟相关信号通路等途径中。通过 WGCNA 构建 lncRNA-mRNA 共表达网络，以 CDKN2B-AS（ANRIL）、CT C-210G5.1.1、RP11-467L20.10.1、RP11-325F22.5.1 和 RP11-59E19.1.1 为 hub DELs。与 miRNAs 一起，构建 ceRNA 网络，功能分析表明，细胞刷状缘和质膜、脂蛋白的合成和运输以及血管紧张素成熟、代谢和血压调节参与了 CD 的进展。我们在临床标本中成功验证了 1 个 lncRNA ANRIL，该 lncRNA 可以在 CD 中显著发挥作用。然而，lncRNA ANRIL 在 CD 预测和诊断中的确切机制还需要进一步探索。
本研究表明，lncRNA ANRIL 对 CD 的发生发展具有一定的预测作用，可能成为新的潜在治疗靶点。
