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Plasma Exosomal MiRNAs Expression Profile in Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis: Case-Control Study and Analysis of Potential Functions
Frontiers in Molecular Neuroscience ( IF 3.5 ) Pub Date : 2020-10-16 , DOI: 10.3389/fnmol.2020.584828
Li-Gang Huang 1, 2 , Yun-He Luo 2 , Ji-Wen Xu 3 , Qin-Chi Lu 3
Affiliation  

Background

To explore an expression profile in plasma exosomal miRNAs of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE + HS) patients and investigate the associated clinical significance and putative pathways involved.

Methods

Plasma exosomal miRNAs were measured in six mTLE + HS patients who were confirmed with pre-surgical stereo-electroencephalography and six without hippocampal sclerosis (mTLE−HS) using Illumina HiSeq 2500. Then six dysregulated miRNAs were chosen for validation in an independent sample of 18 mTLE + HS patients and 18 mTLE−HS controls using RT-qPCR. Receiver operating characteristic curve was conducted to evaluate the diagnostic value of miRNAs in HS. Bioinformatic analyses were conducted to reveal in which pathways these miRNAs were involved.

Results

We revealed that a total of 42 exosomal miRNAs were differentially expressed in mTLE + HS. Among them, 25 were increased and 17 decreased. After validation, hsa-miR-129-5p, -214-3p, -219a-5p, and -34c-5p were confirmed as being upregulated, while hsa-miR-421 and -184 were significantly downregulated in mTLE + HS. Moreover, hsa-miR-184 had the best diagnostic value for discriminating mTLE + HS with 88.9% sensitivity and 83.3% specificity. These six miRNAs regulated several genes from neurotrophin-, hippo-, p53-, TGF- beta-, HIF- 1-, mTOR-related pathways.

Conclusion

Six miRNAs were dysregulated in mTLE + HS patients and targeted several genes. This result might facilitate pathological mechanistic studies of miRNAs in HS and represent potential diagnostic biomarkers. These provided the rationale for further confirmation studies in larger cohorts of prospective patients.



中文翻译:

海马硬化伴颞叶内侧癫痫的血浆外泌体 miRNA 表达谱:病例对照研究和潜在功能分析

Background

探讨颞叶内侧癫痫伴海马硬化 (mTLE + HS) 患者血浆外泌体 miRNA 的表达谱,并研究相关的临床意义和所涉及的推定途径。

Methods

使用 Illumina HiSeq 2500 在 6 名 mTLE + HS 患者中测量了血浆外泌体 miRNA,这些患者通过术前立体脑电图和 6 名没有海马硬化 (mTLE-HS) 的患者进行了测量。然后选择了 6 种失调的 miRNA 在 18 个独立样本中进行验证使用 RT-qPCR 的 mTLE + HS 患者和 18 个 mTLE-HS 对照。采用受试者工作特征曲线评价 miRNAs 在 HS 中的诊断价值。进行生物信息学分析以揭示这些miRNA参与的途径。

Results

我们发现共有 42 种外泌体 miRNA 在 mTLE + HS 中差异表达。其中,增加25家,减少17家。经验证,hsa-miR-129-5p、-214-3p、-219a-5p 和 -34c-5p 被确认为上调,而 hsa-miR-421 和 -184 在 mTLE + HS 中显着下调。此外,hsa-miR-184 对鉴别 mTLE + HS 具有最佳诊断价值,敏感性为 88.9%,特异性为 83.3%。这六种 miRNA 调节来自神经营养因子-、河马-、p53-、TGF-β-、HIF-1-、mTOR 相关途径的几个基因。

Conclusion

六种 miRNA 在 mTLE + HS 患者中失调并靶向几个基因。这一结果可能有助于 HS 中 miRNA 的病理机制研究,并代表潜在的诊断生物标志物。这些为在更大的前瞻性患者队列中进行进一步确认研究提供了依据。

更新日期:2020-11-09
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