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环状 RNA hsa_circITGA4/miR-1468/EGFR/PTEN 在胶质母细胞瘤发生发展中的调控作用及其机制研究。

Hsa_circITGA4/ miR-1468/EGFR/ PTEN a Master Regulators Axis in Glioblastoma Development and Progression.

机构信息

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Tech Royan Institute for Stem Cell Biology and Technology, Tehran, Iran.

出版信息

Mol Biotechnol. 2024 Jan;66(1):90-101. doi: 10.1007/s12033-023-00735-w. Epub 2023 Apr 8.

Abstract

In the fight against glioblastoma, circular RNA is emerging as a functional molecule. However, how circular RNA (circRNA) is regulated and what role it plays is still a mystery. In this research, different bioinformatics approaches were used to evaluate glioblastoma circRNA sequencing and array data, with the goal of developing a putative molecular sponge mechanism control network. The circRNAs were obtained from the Gene Expression Omnibus datasets. MicroRNA-circRNA interactions were predicted using CircInteractome. The microRNAs' expression and survival trends were screened using the TCGA database. MicroRNA gene targets were predicted using the MiRnet database. Sponge network gene candidates were screened using data from the GEPIA. The roles of the targeted genes were to be explained by analyzing data from Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. To build the network and display the outcomes, we utilized python program, and enrichment online Bioinformatics databases. The circRNAs hsa_circITGA4_002, hsa_circITGA4_001, hsa_circITGA4_003, hsa_circ_0030855, hsa_circ_0030857 were chosen from among GBM patients and control group. Upregulation of hsa-miR-1468, hsa-miR-3683, hsa-miR-1273c, and hsa-miR-4665-3p were associated with a poor prognosis in GBM. MicroRNA targets such as ITGA4, LAMA2, EGFR, PTEN, COL1A4, and NCAM2 were analyzed using expression and survival data. The Apoptosis, cell adhesion molecules, PI3K/AKT and P53 signaling pathways were the most abundant functional categories among gene targets. The circRNA molecular sponge regulatory network includes hsa-miR-1468 and hsa-miR-4665-3p. In this network, hs hsa_circITGA4_002, hsa_circITGA4_001, hsa_circ_0030857, EGFR, PTEN, and ITGA4 may represent GBM therapeutic targets. Their role in GBM needs additional study.

摘要

在对抗神经胶质瘤的过程中,环状 RNA 作为一种功能性分子崭露头角。然而,环状 RNA(circRNA)是如何被调控的以及它扮演着什么样的角色,仍然是一个谜。在这项研究中,我们使用了不同的生物信息学方法来评估神经胶质瘤 circRNA 测序和芯片数据,旨在开发一个潜在的分子海绵机制调控网络。circRNAs 从基因表达综合数据库(GEO)中获得。利用 CircInteractome 预测 microRNA-circRNA 相互作用。利用 TCGA 数据库筛选 microRNA 的表达和生存趋势。利用 MiRnet 数据库预测 microRNA 基因靶点。利用 GEPIA 中的数据筛选海绵网络基因候选物。通过分析基因本体论(GO)和京都基因与基因组百科全书(KEGG)的数据来解释靶向基因的作用。为了构建网络并展示结果,我们使用了 python 程序和富集在线生物信息学数据库。从 GBM 患者和对照组中选择了 hsa_circITGA4_002、hsa_circITGA4_001、hsa_circITGA4_003、hsa_circ_0030855 和 hsa_circ_0030857 这四个环状 RNA。hsa-miR-1468、hsa-miR-3683、hsa-miR-1273c 和 hsa-miR-4665-3p 的上调与 GBM 患者的不良预后相关。利用表达和生存数据分析了 microRNA 靶点,如 ITGA4、LAMA2、EGFR、PTEN、COL1A4 和 NCAM2。基因靶点中最丰富的功能类别是细胞凋亡、细胞黏附分子、PI3K/AKT 和 P53 信号通路。环状 RNA 分子海绵调控网络包括 hsa-miR-1468 和 hsa-miR-4665-3p。在这个网络中,hsa_circITGA4_002、hsa_circITGA4_001、hsa_circ_0030857、EGFR、PTEN 和 ITGA4 可能代表着 GBM 的治疗靶点。它们在 GBM 中的作用需要进一步研究。

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