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LncRNA ILF3AS1, MMP3, and MMP9 as well as miRNA-212 as emerging novel biomarkers for childhood epilepsy
Amena Rezk Mohammed1, Wafaa Abdelaziz Emam1, Shaymaa A Mohammed2
1Biochemistry Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
Insights
This study found higher levels of ILF3AS1, MMP3, and MMP9, and lower levels of miRNA-212 in children with epilepsy. These biomarkers show promise for predicting and monitoring pediatric epilepsy.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Neurology
Background:
- Epilepsy affects millions globally, with infants being a significant demographic.
- Understanding epilepsy pathophysiology is crucial for early detection and management.
- Interleukin enhancer binding factor 3 antisense RNA 1 (ILF3AS1), a long non-coding RNA, is implicated in epileptogenesis by upregulating matrix metalloproteinase 3 (MMP3) and MMP9.
Purpose of the Study:
- To evaluate serum levels of ILF3AS1, MMP3, MMP9, and microRNA-212 (miRNA-212) as potential biomarkers in pediatric epilepsy.
- To correlate these molecular markers with magnetic resonance imaging (MRI) findings in children with epilepsy.
Main Methods:
- Quantitative real-time polymerase chain reaction (qPCR) was used to measure serum ILF3AS1 and miRNA-212 levels.
- Enzyme-linked immunosorbent assay (ELISA) determined serum MMP3 and MMP9 concentrations.
- Comparison was made between 50 children with epilepsy and 50 healthy controls, alongside MRI and biochemical data.
Main Results:
- Children with epilepsy exhibited significantly elevated ILF3AS1, MMP3, and MMP9 levels, alongside decreased miRNA-212 levels compared to controls.
- miRNA-212 fold-change was a significant negative predictor of epilepsy (odds ratio = 0.153, p = 0.000).
- Receiver operating characteristic (ROC) analysis indicated high predictive accuracy for these biomarkers, particularly miRNA-212 (Area Under Curve = 0.965).
- Brain lesions were identified in 30% of epilepsy patients via MRI.
Conclusions:
- Elevated serum ILF3AS1, associated with MMP3/MMP9 upregulation and miRNA-212 downregulation, suggests predictive value in pediatric epilepsy.
- The ILF3AS1/miRNA-212/MMP3/MMP9 pathway presents a potential therapeutic target for epilepsy treatment.
- These biomarkers may aid in monitoring epilepsy development and guiding treatment strategies.
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, 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.
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.
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