LncRNA ILF3AS1、MMP3 和 MMP9 以及 miRNA-212 作为儿童癫痫的新兴生物标记物

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2024-08-23 DOI:10.3389/fmolb.2024.1434023

Amena Rezk Mohammed, Wafaa Abdelaziz Emam, Shaymaa A. Mohammed, Alshaymaa A. Abd Elalim, Eatemad Nabil Abdelhalim Mansour, Haidy Mahmoud Nasr, Aya A. Ghamry, Sabah M. Alkhawagah, Doaa Sadek Ahmed Fathy, Rasha Sobhy Elattar, Yasser Gaber Ibrahim Abish, Abdullah Hussein, Boshra Ahmed Zaghloul, Marwa K. Khairallah, Norah Alharbi, Salwa Seif Eldin, Amal Fahmy Dawood, Marwa A. Sabet, Marwa G. Gamea, Suzan Eid Elshishtawy Ibrahim, Aliaa A. Mosa, Marwa A. Dahpy

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引用次数: 0

摘要

背景全球约有 7000 万人患有癫痫。婴儿在这些病例中占很大比例。因此，亟需通过实验室和放射学方法更好地了解癫痫的病理生理学，以便及早发现和优化治疗。白细胞介素增强子结合因子 3 反义 RNA l（ILF3AS1）是一种长非编码 RNA（lncRNA），可增强基质金属蛋白酶 3（MMP3）和基质金属蛋白酶 9（MMP9）的表达，而这两种酶被认为具有致痫作用。目的我们旨在评估lncRNAs ILF3AS1、MMP3和MMP9以及microRNA-212（miRNA-212）作为癫痫患儿预测性生物标志物的血清表达；我们还评估了它们与磁共振成像（MRI）结果的相关性。血清中 lncRNA ILF3AS1 和 miRNA-212 的表达量通过实时定量聚合酶链反应（qPCR）进行评估。结果表明，与对照组相比，癫痫患儿的lncRNA ILF3AS1、MMP3和MMP9水平明显较高，而miRNA-212水平较低。miRNA-212 的折叠变化是一个显著的负预测因子（几率=0.153，P=0.000）。接收者操作特征曲线（Roc）显示，MMP3、MMP9和lncRNA ILF3AS1的曲线下面积以及miRNA-212的折叠变化分别为0.659、0.738、0.656和0.965。15 名癫痫患者（30%）检测到脑部病变，其余 35 名患者（70%）结果正常。结论癫痫患儿血清中lncRNA ILF3AS1的水平高于对照组，并且与MMP3和MMP9的上调以及miRNA-212表达的下调有关，这表明它们在监测癫痫发展方面具有预测作用；这也意味着以ILF3AS1/miRNA-212/MMP3/MMP9轴为重点的治疗方案可能是治疗癫痫的有效策略。

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LncRNAs ILF3AS1, MMP3, and MMP9 as well as miRNA-212 as emerging novel biomarkers for childhood epilepsy

BackgroundGlobally, approximately 70 million people suffer from epilepsy. Infants constitute a significant percentage of these cases. Hence, there is a significant need for better understanding of the pathophysiology of epilepsy through laboratory and radiological methods for early detection and optimized management. Interleukin enhancer binding factor 3 antisense RNA l (ILF3AS1) is a long non-coding RNA (lncRNA) that enhances the expressions of matrix metalloproteinase 3 (MMP3) and matrix metalloproteinase 9 (MMP9), which are considered to be epileptogenic.AimWe aimed to assess the serum expressions of the lncRNAs ILF3AS1, MMP3, and MMP9 along with microRNA-212 (miRNA-212) as predictive biomarkers in children with epilepsy; we also assessed their correlations with magnetic resonance imaging (MRI) findings.Subjects and MethodsFifty children with epilepsy and fifty healthy controls were considered in this study. Serum expressions of the lncRNA ILF3AS1 and miRNA-212 were estimated by quantitative real-time polymerase chain reaction (qPCR). Serum concentrations of MMP3 and MMP9 were estimated by enzyme-linked immunosorbent assay (ELISA) in parallel with MRI findings and different baseline biochemical parameters of all the subjects.ResultsThe results showed significantly higher levels of lncRNAs ILF3AS1, MMP3, and MMP9 as well as lower levels of miRNA-212 in children with epilepsy compared to the controls. The fold-change of miRNA-212 was a significant negative predictor (odds ratio = 0.153, p = 0.000). The receiver operating characteristic curves (Roc) showed that the areas under the curves for MMP3, MMP9, and lncRNA ILF3AS1 as well as the fold-change for miRNA-212 were 0.659, 0.738, 0.656, and 0.965, respectively. Brain lesions were detected in 15 patients (30%) with epilepsy, whereas the remaining 35 patients (70%) had normal results.ConclusionSerum levels of the lncRNA ILF3AS1 among children with epilepsy were higher than those in the control group and were associated with upregulation of both MMP3 and MMP9 as well as downregulation of miRNA-212 expressions, suggesting their predictive utility in monitoring the development of epilepsy; this also means that a treatment plan focusing on the ILF3AS1/miRNA-212/MMP3/MMP9 axis could be an effective strategy for treating epilepsy.

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.