揭示自身免疫性胰腺炎新的外泌体特异性miRNA标记和潜在的分子机制。

IF 3.4 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics Pub Date : 2025-06-05 DOI:10.1016/j.ygeno.2025.111068

Yamin Lai , Mengmeng Shang , Hong Yang , Hong Lv , Panpan Zhang , Tao Guo , Wen Zhang , Aiming Yang , Jia Yu , Jiaming Qian , Dong Wu

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引用次数: 0

摘要

背景：自身免疫性胰腺炎（AIP）是一种罕见的疾病，有时难以诊断。本研究旨在鉴定可作为1型AIP新生物标志物的外泌体mirna。方法：我们从AIP、慢性胰腺炎（CP）、胰腺癌和健康对照个体的外泌体中提取mirna。为了鉴定与AIP相关的差异表达miRNAs (DEmiRNAs)，进行了第二代测序和差异表达分析。然后进行靶基因预测、免疫相关性分析、功能注释以及lncRNA-miRNA-mRNA和转录因子(TF)-miRNA-mRNA网络的构建。最后对中心DEmiRNA进行qPCR分析和ROC评价。结果：外泌体miRNAs在1型AIP患者中表现出特异性表达谱。鉴定出差异表达的靶基因PLXNA2和PGM3，以及与hsa-miR-30b-5p相关的差异表达lncRNA MALAT1。KEGG分析显示PLXNA2在轴突引导中富集。Pearson相关分析显示PLXNA2、PGM3与活化的CD4 T细胞、1型 T辅助细胞等免疫细胞呈显著负相关。TF- mirna - mrna调控网络显示FOXA1是PLXNA2和PGM3的TF， RUNX2是PLXNA2的TF。此外，FOXA1和RUNX2也是hsa-miR-30b-5p的靶基因。结论：从外泌体中鉴定出的Hsa-miR-30b-5p可能是1型AIP特异性的miRNA标记物，因此有可能作为一种新的生物标志物。

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Uncovering novel exosome-specific miRNA markers and potential molecular mechanisms in autoimmune pancreatitis

Background

Autoimmune pancreatitis (AIP) is a rare disease and sometimes difficult to make a diagnosis. This study aimed to identify exosomal miRNAs that could serve as novel biomarkers of type 1 AIP.

Methods

We extracted miRNAs from the exosomes of patients with AIP, chronic pancreatitis (CP), pancreatic cancer, and healthy control individuals. To identify differentially expressed miRNAs (DEmiRNAs) associated with AIP, second-generation sequencing and differential expression analysis were performed. Target gene prediction, immune correlation analysis, functional annotation, and construction of lncRNA-miRNA-mRNA and transcription factor (TF)-miRNA-mRNA networks were then performed. Finally, qPCR analysis and ROC evaluation were performed for hub DEmiRNA.

Results

Exosomal miRNAs exhibited specific expression profiles in patients with type 1 AIP. The differentially expressed target genes PLXNA2 and PGM3, and the differentially expressed lncRNA MALAT1 associated with hsa-miR-30b-5p were identified. KEGG analysis showed that PLXNA2 was enriched in the axon guidance. Pearson's correlation analysis showed that PLXNA2 and PGM3 were significantly negatively correlated with activated CD4 T cells, type 1 T helper cells and other immune cells. The TF-miRNA-mRNA regulatory network showed that FOXA1 was a TF for PLXNA2 and PGM3, and RUNX2 was a TF for PLXNA2. Moreover, FOXA1 and RUNX2 were also the target genes of hsa-miR-30b-5p.

Conclusion

Hsa-miR-30b-5p identified from exosomes may be a miRNA marker specific to type 1 AIP and therefore has the potential to serve as a novel biomarker.

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来源期刊

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.