Sun Zefang, Zhou Rui, Ning Caihong, Zhu Shuai, Li Xueguang, He Quanyuan, Huang Gengwen
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, School of Medicine, Hunan Normal University, Changsha, China.
Pancreas. 2025 Jul 1;54(6):e512-e523. doi: 10.1097/MPA.0000000000002421.
The exact pathogenesis of acute pancreatitis (AP) remains unclear. A ceRNA profile based on single-cell RNA-seq (scRNA-seq) and bulk RNA-seq analysis will deepen our understanding of the mechanisms in AP and identify new potential biomarkers.
The differentially expressed lncRNA (DElncRNA) and mRNA (DEmRNA) were identified using bulk RNA-seq data. The interactions across miRNA and lncRNA/mRNA were integrated to construct a ceRNA network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to analyze the function and pathways. Meanwhile, scRNA-seq analysis was used to evaluate the expression of genes. In addition, immune cell infiltration was also evaluated and the correlation analysis was used to assess the relationship between candidate lncRNAs and immune-related genes.
A ceRNA network that contains 6 DElncRNAs, 38 miRNAs, and 215 DEmRNAs was constructed. A total of 5 candidate mRNAs and 5 candidate lncRNAs were identified. Pathway analysis suggested the candidate genes are associated with calcium-related regulation. scRNA-seq analysis indicated that 5 candidate mRNAs (Afdn, Pik3r1, Ap1s1, Cryab, and Sel1l) may be involved in the pathogenesis of AP by influencing calcium signaling. Immune infiltration analysis found that mice with AP are highly infiltrated with M1 macrophage, monocyte, and CD4+ memory T cells. In quantitative real-time PCR (qRT-PCR) validation, all candidate mRNAs and most candidate lncRNAs displayed consistent expression trends.
The comprehensive analysis of the ceRNA network identified novel genes may regulate calcium-related pathways and participate in the immunomodulation in AP.Trial registration: Not applicable.
急性胰腺炎（AP）的确切发病机制仍不清楚。基于单细胞RNA测序（scRNA-seq）和批量RNA测序分析的ceRNA图谱将加深我们对AP发病机制的理解，并识别新的潜在生物标志物。
利用批量RNA测序数据鉴定差异表达的长链非编码RNA（DElncRNA）和信使核糖核酸（DEmRNA）。整合miRNA与lncRNA/mRNA之间的相互作用以构建ceRNA网络。进行基因本体论和京都基因与基因组百科全书分析以分析功能和通路。同时，利用scRNA-seq分析评估基因表达。此外，还评估了免疫细胞浸润，并采用相关性分析评估候选lncRNA与免疫相关基因之间的关系。
构建了一个包含6个DElncRNA、38个miRNA和215个DEmRNA的ceRNA网络。共鉴定出5个候选mRNA和5个候选lncRNA。通路分析表明候选基因与钙相关调节有关。scRNA-seq分析表明，5个候选mRNA（Afdn、Pik3r1、Ap1s1、Cryab和Sel1l）可能通过影响钙信号传导参与AP的发病机制。免疫浸润分析发现，AP小鼠中M1巨噬细胞、单核细胞和CD4 + 记忆T细胞高度浸润。在定量实时聚合酶链反应（qRT-PCR）验证中，所有候选mRNA和大多数候选lncRNA均呈现一致的表达趋势。
ceRNA网络的综合分析鉴定出的新基因可能调节钙相关通路并参与AP的免疫调节。试验注册：不适用。
