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内侧颞叶癫痫中靶向神经炎症的环状 RNA 相关 ceRNA 网络的综合分析。

Integrated analysis of circRNA- related ceRNA network targeting neuroinflammation in medial temporal lobe epilepsy.

机构信息

The Second Affiliated Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China.

Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250000, China.

出版信息

Brain Res Bull. 2024 Apr;209:110908. doi: 10.1016/j.brainresbull.2024.110908. Epub 2024 Feb 23.

Abstract

BACKGROUND

medial temporal lobe epilepsy (mTLE) is among the most common types of temporal lobe epilepsy (TLE) ,it is generally resistant to drug treatment, which significantly impacts the quality of life and treatment. Research on novel therapeutic approaches for mTLE has become a current focus. Our study aims to construct and analyze a competing endogenous RNA (ceRNA) network that targets neuroinflammation using publicly available data, which may offer a novel therapeutic approach for mTLE.

METHODS

we utilized the R package to analyze GSE186334 downloaded from Gene Expression Omnibus database, subsequently constructing and identifying hub network within the ceRNA network using public databases. Lastly, we validated the expressions and interactions of some nodes within the hub ceRNA network in Sombati cell model.

RESULTS

our transcriptome analysis identified 649 differentially expressed (DE) mRNAs (273 up-regulated, 376 down-regulated) and 36 DE circRNAs (11 up-regulated, 25 down-regulated) among mTLE patients. A total of 23 candidate DE mRNAs associated with neuroinflammation were screened, and two ceRNA networks were constructed. A hub network was further screened which included 3 mRNAs, 22 miRNAs, and 11 circRNAs. Finally, we confirmed the hsa-miR-149-5p is crucial in the regulatory effect of hsa_circ_0005145 on IL - 1α in the hub network.

CONCLUSIONS

In summary, our study identified a hub ceRNA network and validated a potential circRNA-miRNA-mRNA axis targeting neuroinflammation. The results of our research may serve as a potential therapeutic target for mTLE.

摘要

背景

内侧颞叶癫痫(mTLE)是最常见的颞叶癫痫(TLE)类型之一,通常对药物治疗有抗性,这显著影响了患者的生活质量和治疗效果。针对 mTLE 的新型治疗方法的研究已成为当前的重点。我们的研究旨在使用公开数据构建和分析靶向神经炎症的竞争内源性 RNA(ceRNA)网络,这可能为 mTLE 提供一种新的治疗方法。

方法

我们使用 R 包分析了从基因表达综合数据库下载的 GSE186334,随后使用公共数据库构建和识别 ceRNA 网络中的枢纽网络。最后,我们在 Sombati 细胞模型中验证了枢纽 ceRNA 网络中一些节点的表达和相互作用。

结果

我们的转录组分析在 mTLE 患者中鉴定了 649 个差异表达(DE)mRNA(273 个上调,376 个下调)和 36 个 DE 环状 RNA(11 个上调,25 个下调)。筛选出与神经炎症相关的 23 个候选 DEmRNA,并构建了两个 ceRNA 网络。进一步筛选出一个枢纽网络,其中包含 3 个 mRNAs、22 个 miRNAs 和 11 个 circRNAs。最后,我们证实 hsa-miR-149-5p 是枢纽网络中 hsa_circ_0005145 对 IL-1α 调控作用的关键。

结论

总之,我们的研究鉴定了一个枢纽 ceRNA 网络,并验证了一个针对神经炎症的潜在环状 RNA-miRNA-mRNA 轴。我们研究的结果可能为 mTLE 提供一个潜在的治疗靶点。

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