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

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

doi:10.3389/fmolb.2024.1434023

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

Front Mol Biosci. 2024 Aug 23:11:1434023. doi: 10.3389/fmolb.2024.1434023. eCollection 2024.

Authors

Amena Rezk Mohammed¹, Wafaa Abdelaziz Emam¹, Shaymaa A Mohammed², Alshaymaa A Abd Elalim², Eatemad Nabil Abdelhalim Mansour³, Haidy Mahmoud Nasr³, Aya A Ghamry⁴, Sabah M Alkhawagah⁴, Doaa Sadek Ahmed Fathy⁵, Rasha Sobhy Elattar⁶, Yasser Gaber Ibrahim Abish⁷, Abdullah Hussein⁸, Boshra Ahmed Zaghloul⁸, Marwa K Khairallah⁹, Norah Alharbi¹⁰, Salwa Seif Eldin¹¹, Amal Fahmy Dawood¹¹, Marwa A Sabet¹², Marwa G Gamea¹³, Suzan Eid Elshishtawy Ibrahim¹⁴, Aliaa A Mosa¹⁵, Marwa A Dahpy^{15

16}

Affiliations

¹ Biochemistry Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
² Clinical Pathology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
³ Pediatrics Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
⁴ Medical Microbiology and Immunology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
⁵ Community and Occupational Medicine Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
⁶ Neurology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
⁷ Radiodiagnosis Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
⁸ Radiodiagnosis and Intervention Radiology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
⁹ Department of Internal Medicine, Faculty of Medicine, Assiut University, Asyut, Egypt.
¹⁰ Internal Medicine Department, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
¹¹ Department of Basic Medical Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
¹² Department of Microbiology and Immunology, Faculty of Pharmacy, Sphinx University, New Assiut, Egypt.
¹³ Department of Pharmacology, Faculty of Medicine, Assiut University, Asyut, Egypt.
¹⁴ Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
¹⁵ Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Assiut University, Asyut, Egypt.
¹⁶ Department of Medical Biochemistry and Molecular Biology, Armed Forces College of Medicine (AFCM), Cairo, Egypt.

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.

Keywords: MMP3; MMP9, magnetic resonance imaging; epilepsy; lncRNA ILF3AS1; miRNA-212.

Copyright © 2024 Mohammed, Emam, Mohammed, Abd Elalim, Mansour, Nasr, Ghamry, Alkhawagah, Fathy, Elattar, Abish, Hussein, Zaghloul, Khairallah, Alharbi, Seif Eldin, Dawood, Sabet, Gamea, Elshishtawy Ibrahim, Mosa and Dahpy.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors thank Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia, for the Researcher Support (project number: PNURSP2024R339) and publication of this article.