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基于生物信息学分析构建多形性胶质母细胞瘤中的环状RNA-微小RNA-信使核糖核酸调控网络

Construction of a circRNA-miRNA-mRNA regulatory network in glioblastoma multiforme based on bioinformatics analysis.

作者信息

Hu Dongpo, Chen Kangjing

机构信息

School of Medical Technology, Shangqiu Medical College, Shangqiu, Henan, China.

出版信息

Medicine (Baltimore). 2025 May 9;104(19):e42392. doi: 10.1097/MD.0000000000042392.

Abstract

This study aimed to investigate the functional roles and molecular regulatory mechanisms of circular RNAs in the development of glioblastoma multiforme. Differentially expressed circular RNAs were identified by integrating RNA sequencing data and circular RNA microarray data from the Gene Expression Omnibus database. CircAtlas and CircInteractome databases were used to predict microRNAs (miRNAs) interacting with these circular RNAs. Survival analysis of the miRNAs was performed using data from the Chinese Glioma Genome Atlas. The miRTarBase database was used to predict miRNA target genes, followed by the construction of a circular RNA-miRNA-messenger RNA regulatory network specific to glioblastoma multiforme. Functional enrichment analysis was carried out using the DAVID website, and protein-protein interaction networks were created using the Search Tool for the Retrieval of Interacting Genes/Proteins website and Cytoscape. Hub genes were identified, and their expression and prognostic relevance in glioblastoma multiforme were further examined. Four differentially expressed circRNAs and 10 associated miRNAs related to glioblastoma multiforme prognosis were identified. Functional enrichment showed the miRNAs target genes were mainly involved in apoptosis, cell cycle regulation and enriched in cancer-related pathways like mitogen-activated protein kinase and PI3K-Akt. Through the circRNA-miRNA-messenger RNA regulatory network and survival analysis, 3 core genes (core hub genes: catenin beta 1, BCL2, nuclear factor kappa B subunit 1) were identified as significantly downregulated in glioblastoma multiforme and associated with patient survival. This study highlights the potential regulatory roles of circular RNAs in glioblastoma multiforme pathogenesis and their involvement in key molecular pathways. The findings offer a theoretical foundation for understanding glioblastoma multiforme development and may facilitate the identification of novel biomarkers for this aggressive cancer.

摘要

本研究旨在探讨环状RNA在多形性胶质母细胞瘤发生发展中的功能作用及分子调控机制。通过整合来自基因表达综合数据库的RNA测序数据和环状RNA微阵列数据,鉴定出差异表达的环状RNA。利用CircAtlas和CircInteractome数据库预测与这些环状RNA相互作用的微小RNA(miRNA)。使用来自中国胶质瘤基因组图谱的数据对miRNA进行生存分析。利用miRTarBase数据库预测miRNA的靶基因,随后构建多形性胶质母细胞瘤特异性的环状RNA-miRNA-信使RNA调控网络。使用DAVID网站进行功能富集分析,并使用基因/蛋白质相互作用检索工具网站和Cytoscape创建蛋白质-蛋白质相互作用网络。鉴定出枢纽基因,并进一步检测它们在多形性胶质母细胞瘤中的表达及预后相关性。鉴定出4种与多形性胶质母细胞瘤预后相关的差异表达环状RNA和10种相关miRNA。功能富集显示,miRNA靶基因主要参与细胞凋亡、细胞周期调控,并富集于丝裂原活化蛋白激酶和PI3K-Akt等癌症相关通路。通过环状RNA-miRNA-信使RNA调控网络和生存分析,鉴定出3个核心基因(核心枢纽基因:连环蛋白β1、BCL2、核因子κB亚基1)在多形性胶质母细胞瘤中显著下调,并与患者生存相关。本研究突出了环状RNA在多形性胶质母细胞瘤发病机制中的潜在调控作用及其参与的关键分子通路。这些发现为理解多形性胶质母细胞瘤的发生发展提供了理论基础,并可能有助于识别这种侵袭性癌症的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/12074040/3cef9fa4743d/medi-104-e42392-g001.jpg

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