AUTHOR=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. TITLE=LncRNAs ILF3AS1, MMP3, and MMP9 as well as miRNA-212 as emerging novel biomarkers for childhood epilepsy JOURNAL=Frontiers in Molecular Biosciences VOLUME=11 YEAR=2024 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1434023 DOI=10.3389/fmolb.2024.1434023 ISSN=2296-889X ABSTRACT=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.