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胰腺癌中 mRNA、miRNA 和信号通路的综合数据分析。

An Integrated Data Analysis of mRNA, miRNA and Signaling Pathways in Pancreatic Cancer.

机构信息

Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Science, Tehran, Iran.

Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Science, P.O. Box 19395-5487, Tehran, Iran.

出版信息

Biochem Genet. 2021 Oct;59(5):1326-1358. doi: 10.1007/s10528-021-10062-x. Epub 2021 Apr 3.

Abstract

Although many genes and miRNAs have been reported for various cancers, pancreatic cancer's specific genes or miRNAs have not been studied precisely yet. Therefore, we have analyzed the gene and miRNA expression profile of pancreatic cancer data in the gene expression omnibus (GEO) database. The microarray-derived miRNAs and mRNAs were annotated by gene ontology (GO) and signaling pathway analysis. We also recognized mRNAs that were targeted by miRNA through the mirDIP database. An integrated analysis of the microarray revealed that only 6 out of 43 common miRNAs had significant differences in their expression profiles between the tumor and normal groups (P value < 0.05 and |log Fold Changes (logFC)|> 1). The hsa-miR-210 had upregulation, whereas hsa-miR-375, hsa-miR-216a, hsa-miR-217, hsa-miR-216b and hsa-miR-634 had downregulation in pancreatic cancer (PC). The analysis results also revealed 109 common mRNAs by microarray and mirDIP 4.1 databases. Pathway analysis showed that amoebiasis, axon guidance, PI3K-Akt signaling pathway, absorption and focal adhesion, adherens junction, platelet activation, protein digestion, human papillomavirus infection, extracellular matrix (ECM) receptor interaction, and riboflavin metabolism played important roles in pancreatic cancer. GO analysis revealed the significant enrichment in the three terms of biological process, cellular component, and molecular function, which were identified as the most important processes associated strongly with pancreatic cancer. In conclusion, DTL, CDH11, COL5A1, ITGA2, KIF14, SMC4, VCAN, hsa-mir-210, hsa-mir-217, hsa-mir-216a, hsa-mir-216b, hsa-mir-375 and hsa-mir-634 can be reported as the novel diagnostic or even therapeutic markers for the future studies. Also, the hsa-mir-107 and hsa-mir-125a-5p with COL5A1, CDH11 and TGFBR1 genes can be introduced as major miRNA and genes on the miRNA-drug-mRNA network. The new regulatory network created in our study could give a deeper knowledge of the pancreatic cancer.

摘要

虽然已经报道了许多与各种癌症相关的基因和 miRNA,但胰腺癌的特定基因或 miRNA 尚未得到精确研究。因此,我们分析了基因表达综合数据库 (GEO) 中胰腺癌数据的基因和 miRNA 表达谱。通过基因本体 (GO) 和信号通路分析对微阵列衍生的 miRNA 和 mRNAs 进行注释。我们还通过 mirDIP 数据库识别了 miRNA 靶向的 mRNAs。通过对微阵列的综合分析,我们发现肿瘤组和正常组之间的 43 个常见 miRNA 中仅有 6 个 miRNA 的表达谱存在显著差异 (P 值<0.05,logFC 绝对值>1)。hsa-miR-210 呈上调表达,而 hsa-miR-375、hsa-miR-216a、hsa-miR-216b 和 hsa-miR-634 在胰腺癌 (PC) 中呈下调表达。分析结果还通过 microarray 和 mirDIP 4.1 数据库揭示了 109 个常见 mRNAs。通路分析显示,变形虫病、轴突导向、PI3K-Akt 信号通路、吸收和黏着斑、黏着连接、血小板激活、蛋白消化、人乳头瘤病毒感染、细胞外基质 (ECM) 受体相互作用以及核黄素代谢在胰腺癌中发挥着重要作用。GO 分析表明,在生物学过程、细胞成分和分子功能这三个术语中存在显著富集,这些术语被确定为与胰腺癌密切相关的最重要过程。总之,DTL、CDH11、COL5A1、ITGA2、KIF14、SMC4、VCAN、hsa-mir-210、hsa-mir-217、hsa-mir-216a、hsa-mir-216b、hsa-mir-375 和 hsa-mir-634 可作为未来研究的新型诊断甚至治疗标志物。此外,与 COL5A1、CDH11 和 TGFBR1 基因相关的 hsa-mir-107 和 hsa-mir-125a-5p 可以作为 miRNA 和 miRNA-药物-mRNA 网络中的主要基因。我们研究中创建的新调控网络可以为深入了解胰腺癌提供更多的知识。

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