人类慢性萎缩性胃炎中与免疫相关的 circRNA 和 mRNA 的特征。

IF 4.2 2区 医学 Q2 IMMUNOLOGY
Journal of Inflammation Research Pub Date : 2024-11-08 eCollection Date: 2024-01-01 DOI:10.2147/JIR.S472213
Yang Chao, Xiya Jin, Rui Guo, Hongyu Zhang, Xueling Cui, Yan Qi
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引用次数: 0

摘要

背景:慢性萎缩性胃炎(CAG)是一种以胃部炎症和适当粘膜腺体丧失为特征的严重疾病。CAG 的发病机制尚不清楚。探索与免疫相关的环状 RNA(circRNA)可为潜在的诊断和治疗策略提供见解:方法:对 40 名 CAG 和非 CAG(CNAG)患者的样本进行了高通量测序,并通过 EdgeR 分析确定了不同表达的 circRNA 和 mRNA。基因本体(GO)分析阐明了生物功能,而免疫细胞丰度识别器(ImmuCellAI)估算了免疫细胞的丰度。流式细胞术分析了免疫细胞浸润情况。加权基因共表达网络分析(WGCNA)确定了与CAG免疫反应相关的枢纽基因。构建了 CircRNA-mRNA 网络,并通过 qRT-PCR 验证了研究结果:结果:在 CAG 和 CNAG 之间共发现了 163 个差异表达的免疫相关基因(DEIRGs)。CAG 中上调的免疫相关 mRNA 在抗微生物体液反应、病毒进入宿主细胞、中性粒细胞活化和白细胞迁移中明显富集。相反,下调的免疫相关 mRNA 与自然杀伤细胞介导的细胞毒性调节、适应性免疫反应的正向调节、抗原受体介导的信号通路和 B 细胞活化有关。免疫细胞丰度识别器(ImmuCellAI)和流式细胞术证实,与 CNAG 相比,CAG 中的中性粒细胞浸润增加。WGCNA 发现了 56 个与免疫相关的中枢基因。此外,还研究了 CNAG 和 CAG 的 circRNA 表达谱,发现 CAG 中有 19 个上调的 circRNA 和 23 个下调的 circRNA。上调的 circRNA 与肉碱代谢过程和 B 细胞受体信号通路调控等生物过程有关。根据与枢纽免疫相关基因高度相关的5个circRNA,构建了一个circRNA-mRNA共表达网络。此外,还验证了八种免疫相关 mRNA 和五种 circRNA 在 CAG 中的表达:本研究首次系统分析了 CAG 中的 circRNA 图谱,为 CAG 治疗中潜在的免疫治疗策略和早期诊断生物标志物提供了重要启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Characterization of Immune-Related circRNAs and mRNAs in Human Chronic Atrophic Gastritis.

Background: Chronic atrophic gastritis (CAG) is a severe condition characterized by inflammation and loss of appropriate mucosal glands in the stomach. The underlying mechanisms of CAG development remain unclear. Exploring immune-related circular RNAs (circRNAs) could provide insights for potential diagnostic and therapeutic strategies.

Methods: Samples from 40 patients with CAG and non-CAG (CNAG) underwent high-throughput sequencing, and EdgeR analysis identified differentially expressed circRNAs and mRNAs. Gene Ontology (GO) analysis elucidated biological functions, while Immune Cell Abundance Identifier (ImmuCellAI) estimated immune cell abundance. Flow cytometry analyzed immune cell infiltration. Weighted gene co-expression network analysis (WGCNA) identified hub genes related to the immune response in CAG. CircRNA-mRNA networks were constructed, and qRT-PCR validated findings.

Results: A total of 163 differentially expressed immune-related genes (DEIRGs) were identified between CAG and CNAG. The upregulated immune-related mRNAs in CAG were significantly enriched in antimicrobial humoral response, viral entry into host cells, neutrophil activation, and leukocyte migration. Conversely, downregulated immune-related mRNAs were linked to regulation of natural killer cell-mediated cytotoxicity, positive regulation of adaptive immune response, antigen receptor-mediated signaling pathway, and B cell activation. Immune Cell Abundance Identifier (ImmuCellAI) and flow cytometry confirmed increased neutrophil infiltration in CAG compared to CNAG. WGCNA identified 56 hub immune-related genes. Additionally, circRNA expression profiles in CNAG and CAG were explored, with 19 upregulated and 23 downregulated circRNAs identified in CAG. The upregulated circRNAs were associated with biological processes like carnitine metabolic process and regulation of B cell receptor signaling pathway. A circRNA-mRNA co-expression network was constructed based on five circRNAs highly related to hub immune-related genes. Furthermore, the expression of eight immune-related mRNAs and five circRNAs were validated in CAG.

Conclusion: This study is the first systematic analysis of circRNA profiles in CAG and provide important insights for potential immunotherapeutic strategies and early diagnostic biomarkers in CAG treatment.

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来源期刊
Journal of Inflammation Research
Journal of Inflammation Research Immunology and Microbiology-Immunology
CiteScore
6.10
自引率
2.20%
发文量
658
审稿时长
16 weeks
期刊介绍: An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.
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