Identification of potential serum exosomal microRNAs involved in acinar-ductal metaplasia that is a precursor of pancreatic cancer associated with chronic pancreatitis.
Identification of potential serum exosomal microRNAs involved in acinar-ductal metaplasia that is a precursor of pancreatic cancer associated with chronic pancreatitis.
复制标题
鉴定参与腺泡导管化生的潜在血清外泌体 microRNA，腺泡导管化生是与慢性胰腺炎相关的胰腺癌的前兆
DOI：
10.1097/md.0000000000025753
复制
发表时间：
2021-05-07
期刊：
影响因子：
1.6
通讯作者：
Ding Z
中科院分区：
文献类型：
--
作者：
Sheng LP;Han CQ;Nie C;Xu T;Zhang K;Li XJ;Xie XR;Lin R;Ding Z
摘要背景：由于慢性胰腺炎（CP）的早期诊断困难，寻找新的检测CP的生物标志物是当务之急。位于血清中的Exosomal microRNAs（Exo-miRNAs）可能是CP潜在的诊断和治疗靶点。目的：对CP患者血清中差异表达的Exo-miRNAs（DE-Exo-miRNAs）进行生物信息学分析。方法：数据集GSE 128508从基因表达综合数据库（GEO）下载。使用BRB-ArrayTools和微阵列显著性分析（SAM）进行分析。通过miRWalk数据库预测DE-S-Exo-miRNAs的靶基因。在Cytoscape软件3.7.0中使用插件CNOGO进行进一步的基因本体（GO）术语和基因组京都百科全书（KEGG）途径分析。随后，使用检索相互作用基因（STRING）数据库的搜索工具进行靶基因编码蛋白之间的相互作用调控网络，并使用插件分子复合物检测（MCODE）和Cytoscape软件3.7.0中的cytoHubba进行分析。结果：共鉴定出227个DE-Exo-miRNAs。使用miRWalk数据库的进一步分析鉴定了这些miRNAs的5164个靶基因。利用STRING数据库和Cytoscape软件构建了hub 10个高度上调的miRNAs和1个下调的miRNAs的1912个潜在靶基因的蛋白质-蛋白质相互作用（PPI）调控网络。利用Cytoscape软件工具进行功能分析，突出了胰腺癌相关的靶基因。胰腺炎性环境中的腺泡导管化生（ADM）是胰腺癌的前兆。随后，我们构建了ADM相关靶基因及其miRNA的网络。结论：血清中exo-miRNAs及其靶基因可能是CP早期诊断和治疗的重要靶点。此外，我们鉴定了参与ADM的潜在Exo-miRNAs，ADM是与CP相关的胰腺癌的前体。
Abstract Backgrounds: Due to difficulty in early diagnosis of chronic pancreatitis (CP), it is urgent to find novel biomarkers to detect CP. Exosomal microRNAs (Exo-miRNAs) located in the serum may be potential diagnostic and therapeutic targets for CP. Objective: To identify differentially expressed Exo-miRNAs (DE-Exo-miRNAs) in the serum of CP patients, we performed a bioinformatics analysis. Methods: The dataset GSE128508 was downloaded from the Gene Expression Omnibus (GEO) database. The analysis was carried out using BRB-ArrayTools and significance analysis of microarrays (SAM). The target genes of DE-S-Exo-miRNAs were predicted by miRWalk databases. Further gene ontology (GO) term and Kyoto Encyclopedia of Genomes (KEGG) pathway analyses were performed with plug-in ClueGO in Cytoscape software 3.7.0. Subsequently, the interaction regulatory network between encoded proteins of target genes was performed with the Search Tool for the Retrieval of Interacting Genes (STRING) database and analyzed using plug-in Molecular Complex Detection (MCODE) and cytoHubba in Cytoscape software 3.7.0. Results: We identified 227 DE-Exo-miRNAs in the serum. Further analysis using the miRWalk database identified 5164 target genes of these miRNAs. The protein–protein interaction (PPI) regulatory network of 1912 potential target genes for hub 10 up-regulated miRNAs with high degrees and one down-regulated miRNAs were constructed using the STRING database and Cytoscape software. The functional analysis using Cytoscape software tool highlighted that target genes involved in pancreatic cancer. Acinar-ductal metaplasia (ADM) in the inflammatory environment of CP is a precursor of pancreatic cancer. Subsequently, we constructed a network of target genes associated with ADM and their miRNAs. Conclusions: Exo-miRNAs in the serum as well as their target genes may be promising targets for the early diagnosis and treatment of CP. In addition, we identified potential Exo-miRNAs involved in ADM that is a precursor of pancreatic cancer associated with CP.