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Published on: August 15, 2017
Identification of miRNA-mRNA regulatory network associated with the glutamatergic system in post-traumatic epilepsy
Xiaoyuan Zhang1,2, Yixun Ma3,4, Fengjuan Zhou1,2
1Key Laboratory of Evidence Science, Institute of Evidence Law and Forensic Science, China University of Political Science and Law, Ministry of Education, Beijing, China.
Background:
Glutamate is one of the most important excitatory neurotransmitters in the mammalian brain and is involved in a variety of neurological disorders. Increasing evidence also shows that microRNA (miRNA) and mRNA pairs are engaged in a variety of pathophysiological processes. However, the miRNA and mRNA pairs that affect the glutamatergic system in post-traumatic epilepsy (PTE) remain unknown.
Methods:
PTE rats were induced by injecting 0.1 mol/L, 1 μL/min FeCl2 solution. Behavioral scores and EEG monitoring were used to evaluate whether PTE was successfully induced. RNA-seq was used to obtain mRNA and miRNA expression profiles. Bioinformatics analysis was performed to screen differentially expressed mRNAs and miRNAs associated with the glutamatergic system and then predict miRNA-mRNA interaction pairs. Real-time quantitative reverse transcription PCR was used to further validate the expression of the differential miRNAs and mRNAs. The microRNA-mRNA was subject to the Pearson correlation analysis.
Results:
Eight of the 91 differentially expressed mRNAs were associated with the glutamatergic system, of which six were upregulated and two were downregulated. Forty miRNAs were significantly differentially expressed, with 14 upregulated and 26 downregulated genes. The predicted miRNA-mRNA interaction network shows that five of the eight differentially expressed mRNAs associated with the glutamatergic system were targeted by multiple miRNAs, including Slc17a6, Mef2c, Fyn, Slc25a22, and Shank2, while the remaining three mRNAs were not targeted by any miRNAs. Of the 40 differentially expressed miRNAs, seven miRNAs were found to have multiple target mRNAs associated with the glutamatergic system. Real-time quantitative reverse transcription PCR validation and Pearson correlation analysis were performed on these seven targeted miRNAs-Slc17a6, Mef2c, Fyn, Slc25a22, and Shank2-and six additional miRNAs selected from the literature. Real-time quantitative reverse transcription PCR showed that the expression levels of the mRNAs and miRNAs agreed with the predictions in the study. Among them, the miR-98-5p-Slc17a6, miR-335-5p-Slc17a6, miR-30e-5p-Slc17a6, miR-1224-Slc25a22, and miR-211-5p-Slc25a22 pairs were verified to have negative correlations.
Conclusions:
Our results indicate that miRNA-mRNA interaction pairs associated with the glutamatergic system are involved in the development of PTE and have potential as diagnostic biomarkers and therapeutic targets for PTE.
Insights
Researchers identified microRNA-mRNA pairs impacting the glutamatergic system in post-traumatic epilepsy (PTE) rats. These interactions offer potential diagnostic biomarkers and therapeutic targets for PTE.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Glutamate is a key excitatory neurotransmitter in the mammalian brain.
- Dysregulation of glutamate is implicated in various neurological disorders.
- MicroRNA (miRNA) and messenger RNA (mRNA) interactions play roles in pathophysiological processes, but their role in post-traumatic epilepsy (PTE) is unclear.
Purpose of the Study:
- To investigate miRNA-mRNA interactions associated with the glutamatergic system in the context of PTE.
- To identify potential diagnostic biomarkers and therapeutic targets for PTE.
Main Methods:
- Post-traumatic epilepsy (PTE) was induced in rats using FeCl2 injection.
- RNA sequencing (RNA-seq) was employed to profile mRNA and miRNA expression.
- Bioinformatics analysis identified differentially expressed genes and predicted miRNA-mRNA interactions.
- Real-time quantitative reverse transcription PCR (RT-qPCR) and Pearson correlation analysis validated key interactions.
Main Results:
- Eight differentially expressed mRNAs related to the glutamatergic system were identified, with six upregulated and two downregulated.
- Forty miRNAs were significantly differentially expressed (14 upregulated, 26 downregulated).
- Specific miRNA-mRNA pairs, including miR-98-5p-Slc17a6, miR-335-5p-Slc17a6, miR-30e-5p-Slc17a6, miR-1224-Slc25a22, and miR-211-5p-Slc25a22, showed significant negative correlations.
Conclusions:
- miRNA-mRNA interactions targeting the glutamatergic system are involved in PTE development.
- These identified miRNA-mRNA pairs represent potential diagnostic biomarkers for PTE.
- The findings suggest these interactions could serve as therapeutic targets for PTE treatment.
