长链非编码RNA ILF3AS1、基质金属蛋白酶3和基质金属蛋白酶9以及微小RNA-212作为儿童癫痫新出现的生物标志物。
LncRNA ILF3AS1, MMP3, and MMP9 as well as miRNA-212 as emerging novel biomarkers for childhood epilepsy.
作者信息
Mohammed Amena Rezk, Emam Wafaa Abdelaziz, Mohammed Shaymaa A, Abd Elalim Alshaymaa A, Mansour Eatemad Nabil Abdelhalim, Nasr Haidy Mahmoud, Ghamry Aya A, Alkhawagah Sabah M, Fathy Doaa Sadek Ahmed, Elattar Rasha Sobhy, Abish Yasser Gaber Ibrahim, Hussein Abdullah, Zaghloul Boshra Ahmed, Khairallah Marwa K, Alharbi Norah, Seif Eldin Salwa, Dawood Amal Fahmy, Sabet Marwa A, Gamea Marwa G, Elshishtawy Ibrahim Suzan Eid, Mosa Aliaa A, Dahpy Marwa A
机构信息
Biochemistry Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
Clinical Pathology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
出版信息
Front Mol Biosci. 2024 Aug 23;11:1434023. doi: 10.3389/fmolb.2024.1434023. eCollection 2024.
BACKGROUND
Globally, 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.
AIM
We 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 METHODS
Fifty 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.
RESULTS
The 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, = 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.
CONCLUSION
Serum 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.
背景
全球约有7000万人患有癫痫。婴儿在这些病例中占相当大的比例。因此，迫切需要通过实验室和放射学方法更好地了解癫痫的病理生理学，以便早期发现和优化治疗。白细胞介素增强子结合因子3反义RNA 1（ILF3AS1）是一种长链非编码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性。
目的
我们旨在评估长链非编码RNA ILF3AS1、MMP3和MMP9以及微小RNA-212（miRNA-212）在癫痫患儿血清中的表达情况，将其作为预测生物标志物；我们还评估了它们与磁共振成像（MRI）结果的相关性。
研究对象与方法
本研究纳入了50例癫痫患儿和50名健康对照。通过定量实时聚合酶链反应（qPCR）评估长链非编码RNA ILF3AS1和miRNA-212的血清表达。通过酶联免疫吸附测定（ELISA）评估MMP3和MMP9的血清浓度，同时观察所有受试者的MRI结果和不同的基线生化参数。
结果
结果显示，与对照组相比，癫痫患儿的长链非编码RNA ILF3AS1、MMP3和MMP9水平显著升高，而miRNA-212水平降低。miRNA-212的变化倍数是一个显著的负向预测指标（优势比=0.153，P=0.000）。受试者工作特征曲线（ROC）显示，MMP3、MMP9和长链非编码RNA ILF3AS1的曲线下面积以及miRNA-212的变化倍数分别为0.659、0.738、0.656和0.965。15例（30%）癫痫患者检测到脑部病变，其余35例（70%）结果正常。
结论
癫痫患儿血清中长链非编码RNA ILF3AS1水平高于对照组，且与MMP3和MMP9的上调以及miRNA-212表达的下调相关，表明它们在监测癫痫发展方面具有预测作用；这也意味着针对ILF3AS1/miRNA-212/MMP3/MMP9轴的治疗方案可能是治疗癫痫的有效策略。
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