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

• Published in: Genomics (San Diego, Calif.) Vol. 117; no. 4; p. 111068
• Main Authors: Lai, Yamin, Shang, Mengmeng, Yang, Hong, Lv, Hong, Zhang, Panpan, Guo, Tao, Zhang, Wen, Yang, Aiming, Yu, Jia, Qian, Jiaming, Wu, Dong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2025
• Subjects: Autoimmune pancreatitis; Autoimmune Pancreatitis - genetics; Autoimmune Pancreatitis - metabolism; Biomarkers - metabolism; Exosome; Exosomes - genetics; Exosomes - metabolism; Female; Gene Regulatory Networks; Hsa-miR-30b-5p; Humans; Immune; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Pancreatic Neoplasms - genetics; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Target genes; Transcription Factors - genetics; Transcription Factors - metabolism; Target genes; Exosome; Autoimmune pancreatitis; Hsa-miR-30b-5p; Immune
• DOI: 10.1016/j.ygeno.2025.111068
• ISSN: 0888-7543; 1089-8646

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. 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. 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. 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. •The hsa-miR-30b-5P identified from exosomes may be a miRNA marker specific to AIP.•The hsa-miR-30b-5P has the potential to serve as a novel biomarker for AIP diagnosis.•The MALAT1-hsa-miR-30b-5P-PLXNA2/PGM3 axis identified based on hsa-miR-30b-5P may play an important role in AIP.