基于GEO数据库筛选慢性胰腺炎恶变过程中关键miRNA和ceRNA网络构建  

Screening of Key miRNAs and Construction of Competing Endogenous RNA Network Involved in the Progression from Chronic Pancreatitis to Pancreatic Cancer Based on GEO Database

作　　者：张立洁 彭泉 ZHANG Li-jie;PENG Quan(Tumor Diagnosis and Treatment Center,901th Hospital of PLA,Hefei 230031,China;Department of General Surgery,901th Hospital of PLA,Hefei 230031,China)

机构地区：[1]解放军第901医院肿瘤中心,合肥230031 [2]解放军第901医院普外科,合肥230031

出　　处：《现代检验医学杂志》2023年第2期18-24,共7页Journal of Modern Laboratory Medicine

基　　金：中国人民解放军联勤保障部队第901医院院管课题(NO.2021YGYB06):ADAM8基因在胰腺癌中的表达及其启动子区甲基化状态相关性研究。

摘　　要：目的筛选慢性胰腺炎(chronic pancreatitis,CP)进展到胰腺癌(pancreatic cancer,PC)过程中发挥潜在作用的miRNA及其调控网络。方法从GEO数据库中下载芯片数据GSE24279和GSE25820,筛选出在CP和PC中差异表达的miRNA(differential expression miRNA,DEM)。预测DEM的靶基因和长链非编码RNA(long non-coding RNA),随后进行靶基因富集分析,构建蛋白互作网络(protein-protein interaction,PPI)并筛选出枢纽基因和具有特殊生物学功能的模块,通过综合分析DEM,枢纽基因和LncRNA的表达和预后,基于竞争性内源RNA(competing endogenous RNAs,ceRNA)的理论,构建miRNA的调控网络。结果筛选出16个DEM,其靶基因参与共生过程,细胞器组织的正调控,细胞质的核周区域和双链RNA结合。从PPI网络中,筛选出17个枢纽基因和3个模块。综合分析后,将hsa-miR-221-3p,hsa-miR-222-3p,hsa-miR-210-3p及RNPS1,MGRN1作为CP进展为PC中关键节点。41个LncRNA结合关键DEM,其中MIAT,DANT2,TTN-AS1,PAXIP1-AS2和LINC00473具有预后价值。综合以上结果,构建出包含3个DEM,2个基因和5个LncRNA的ceRNA调控网络。结论研究采用的整合分析方法有助于揭示CP恶变的机制,构建的LncRNA-miRNA-基因调控网络,为预测和治疗由CP进展为PC的患者提供了新的生物学靶点。Objective To find the key miRNAs and their potential molecular mechanisms in the progression from chronic pancreatitis(CP)to pancreatic cancer(PC).Methods Microarray data GSE24279 and GSE25820 were downloaded from Gene Expression Omnibus(GEO)database,and screened out the differential expressed miRNAs(DEM)in CP and PC.Predicted the target gene and LncRNAs(long non-coding RNA)of DNA,and then carried out the enrichment analysis of target genes,constructed the Protein-protein interaction(PPI)and screened out the hinge genes and modules with special and prognosis of DEM,hinge genes and LncRNA,built the miRNA regulatory network based on the theory of competitive endogenous RNAs(ceRNA).Results 16 DEM were found both in GSE24279 and GSE25820,enrichment analyses showed that targets of overlapped DEM were significantly enriched in symbiont process,positive regulation of organelle organization,perinuclear region of cytoplasm and double-stranded RNA binding.From the PPI network,17 nodes and 3 modules were selected.According to the expression and prognostic,3 upregulated DEM(hsa-miR-221-3p,hsa-miR-222-3p,hsa-miR-210-3p)and 2 target genes(RNPS1 and MGRN1)were screened,subsequently,41 LncRNAs were explored to potentiality bind to those 3 key DEM,5 of them(MIAT,DANT2,TTN-AS1,PAXIP1-AS2 and LINC00473)had the positive prognostic value.Finally,constructed a regulatory network based on competing endogenous RNA(ceRNA)hypothesis.Conclusion The methodology in this study contributed to understanding the pathogenesis involved in the progression from CP to PC,the novel LncRNA-miRNA-gene regulatory network can provide new clues to predict the development of PC in CP patients.

关 键 词：胰腺癌 慢性胰腺炎 微小RNA 竞争性内源RNA 

分 类 号：R735.9[医药卫生—肿瘤] R730.43[医药卫生—临床医学]