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乳腺癌中潜在功能 circRNA-miRNA-mRNA 网络的生物信息学分析。

Bioinformatics analysis of the potentially functional circRNA-miRNA-mRNA network in breast cancer.

机构信息

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

出版信息

PLoS One. 2024 Apr 18;19(4):e0301995. doi: 10.1371/journal.pone.0301995. eCollection 2024.

Abstract

Breast cancer (BC) is the most common cancer among women with high morbidity and mortality. Therefore, new research is still needed for biomarker detection. GSE101124 and GSE182471 datasets were obtained from the Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (circRNAs). The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used to identify the significantly dysregulated microRNAs (miRNAs) and genes considering the Prediction Analysis of Microarray classification (PAM50). The circRNA-miRNA-mRNA relationship was investigated using the Cancer-Specific CircRNA, miRDB, miRTarBase, and miRWalk databases. The circRNA-miRNA-mRNA regulatory network was annotated using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. The protein-protein interaction network was constructed by the STRING database and visualized by the Cytoscape tool. Then, raw miRNA data and genes were filtered using some selection criteria according to a specific expression level in PAM50 subgroups. A bottleneck method was utilized to obtain highly interacted hub genes using cytoHubba Cytoscape plugin. The Disease-Free Survival and Overall Survival analysis were performed for these hub genes, which are detected within the miRNA and circRNA axis in our study. We identified three circRNAs, three miRNAs, and eighteen candidate target genes that may play an important role in BC. In addition, it has been determined that these molecules can be useful in the classification of BC, especially in determining the basal-like breast cancer (BLBC) subtype. We conclude that hsa_circ_0000515/miR-486-5p/SDC1 axis may be an important biomarker candidate in distinguishing patients in the BLBC subgroup of BC.

摘要

乳腺癌(BC)是女性中发病率和死亡率较高的最常见癌症。因此,仍需要新的研究来进行生物标志物检测。从基因表达综合数据库(GEO)中获取 GSE101124 和 GSE182471 数据集,以评估差异表达的环状 RNA(circRNA)。使用癌症基因组图谱(TCGA)和乳腺癌国际联合会分子分类(METABRIC)数据库,考虑到预测分析微阵列分类(PAM50),确定显著失调的 microRNAs(miRNAs)和基因。使用癌症特异性环状 RNA、miRDB、miRTarBase 和 miRWalk 数据库研究 circRNA-miRNA-mRNA 关系。使用基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)途径数据库注释 circRNA-miRNA-mRNA 调控网络。通过 STRING 数据库构建蛋白质-蛋白质相互作用网络,并使用 Cytoscape 工具可视化。然后,根据 PAM50 亚组中特定的表达水平,使用一些选择标准筛选原始 miRNA 数据和基因。使用 cytoHubba Cytoscape 插件的瓶颈方法获得高度相互作用的枢纽基因。对这些在我们的研究中位于 miRNA 和 circRNA 轴上的枢纽基因进行无病生存和总生存分析。我们鉴定了三个 circRNA、三个 miRNA 和十八个候选靶基因,它们可能在 BC 中发挥重要作用。此外,已经确定这些分子可用于 BC 的分类,特别是在确定基底样乳腺癌(BLBC)亚型方面。我们得出结论,hsa_circ_0000515/miR-486-5p/SDC1 轴可能是区分 BC 中 BLBC 亚组患者的重要生物标志物候选物。

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