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分析与慢传输型便秘相关的差异表达长链非编码 RNA 和信使 RNA。

Analysis of differentially expressed lncRNAs and mRNAs associated with slow‑transit constipation.

机构信息

Research Institute of Agricultural Biotechnology, Jingchu University of Technology, Jingmen 448000, China.

Clinical Medical Research Center for Functional Colon Diseases of Hubei Province, Jingmen Central Hospital, Hubei Province, China.

出版信息

Gene. 2024 Jul 1;914:148400. doi: 10.1016/j.gene.2024.148400. Epub 2024 Mar 26.

DOI:10.1016/j.gene.2024.148400
PMID:38527672
Abstract

Slow transit constipation (STC) is a refractory gastrointestinal disease, accounting for approximately 13 ∼ 37 % of chronic constipation. However, the molecular mechanism of STC remains poorly understood. Herein, this study aims to identify the key mRNAs and lncRNAs associated with STC. To this end, we performed high-throughput RNA sequencing to identify differentially expressed (DE) mRNAs and lncRNAs in the whole-layer sigmoid intestinal tissues from 4 STC patients and 4 non-STC patients. The identified DE lncRNAs and mRNAs were validated through quantitative real-time PCR. Weighted gene co-expression network analysis (WGCNA) and Pearson correlation analysis were conducted to determine the significantly correlated DE mRNA-lncRNA pairs. A total of 1420 DE lncRNAs and 1634 DE mRNAs were identified. Kyoto Encyclopedia of Genes and Genomes analysis of DE mRNAs indicated that these DE mRNAs might be associated with systemic lupus erythematosus, alcoholism, intestinal immune network for IgA production, inflammatory bowel disease, NF-kappa B signaling pathway. WGCNA and Pearson correlation analyses jointly identified 16,577 significantly correlated DE mRNA-lncRNA pairs. Furthermore, lncRNAs LINC00641, LINC02268, LINC03013 were identified as hub lncRNAs. The protein-protein interaction (PPI) network of proteins encoded by DE mRNAs was established, and PPI-based analysis revealed that Interleukin 2(IL2), CD80 molecule (CD80), interleukin-17A (IL-17A) might play significant roles in the development of STC. This study analyzes the expression profiles of lncRNAs and mRNAs associated with STC. Our findings will contribute to further understanding of the molecular mechanism of STC and provide potential diagnostic or therapeutic biomarkers for STC.

摘要

慢传输型便秘(STC)是一种难治性胃肠道疾病,约占慢性便秘的 13%~37%。然而,STC 的分子机制仍知之甚少。本研究旨在鉴定与 STC 相关的关键 mRNA 和 lncRNA。为此,我们对 4 例 STC 患者和 4 例非 STC 患者的全层乙状结肠组织进行了高通量 RNA 测序,以鉴定差异表达(DE)的 mRNA 和 lncRNA。通过实时定量 PCR 验证了鉴定出的 DE lncRNA 和 mRNA。进行加权基因共表达网络分析(WGCNA)和 Pearson 相关分析,以确定显著相关的 DE mRNA-lncRNA 对。共鉴定出 1420 个 DE lncRNA 和 1634 个 DE mRNA。DE mRNA 的京都基因与基因组百科全书(KEGG)分析表明,这些 DE mRNA 可能与系统性红斑狼疮、酒精中毒、肠黏膜免疫 IgA 产生、炎症性肠病、NF-kappa B 信号通路有关。WGCNA 和 Pearson 相关分析联合鉴定出 16577 个显著相关的 DE mRNA-lncRNA 对。此外,lncRNA LINC00641、LINC02268、LINC03013 被鉴定为枢纽 lncRNA。构建了 DE mRNA 编码蛋白的蛋白质-蛋白质相互作用(PPI)网络,基于 PPI 的分析表明白细胞介素 2(IL2)、CD80 分子(CD80)、白细胞介素 17A(IL-17A)可能在 STC 的发生发展中发挥重要作用。本研究分析了与 STC 相关的 lncRNA 和 mRNA 的表达谱。我们的发现将有助于进一步了解 STC 的分子机制,并为 STC 提供潜在的诊断或治疗生物标志物。

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