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A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy
Published on: November 13, 2016
Integrative analysis of expression profile indicates the ECM receptor and LTP dysfunction in the glioma-related
Zhi-Bin Wang1,2, Jian Qu3, Pan Xie1,2
1Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China.
Background:
Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive.
Objective:
To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients.
Methods:
Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor.
Results:
We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease's progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance.
Conclusion:
These findings can offer a fresh perspective on GRE-induced brain network changes.
Insights
This study reveals key microRNA, mRNA, and lncRNA changes in glioma-related epilepsy (GRE), offering new insights into brain network alterations and potential therapeutic targets for epilepsy in glioma patients.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Seizures are a frequent complication in glioma patients, leading to neurological dysfunction.
- The precise mechanisms underlying brain network alterations in glioma-related epilepsy (GRE) remain unclear.
Purpose of the Study:
- To elucidate the pathogenic mechanisms of GRE by analyzing dynamic microRNA, mRNA, and lncRNA expression profiles.
- To identify potential molecular targets for understanding and treating GRE.
Main Methods:
- Comparative analysis of brain tissue from 16 GRE patients and 9 glioma without epilepsy (GNE) patients.
- High-throughput microarray analysis of miRNA, lncRNA, and mRNA expression.
- Bioinformatic analysis using R and Bioconductor to identify differentially expressed molecules and pathways.
Main Results:
- Identified 3 differentially expressed miRNAs, 6 lncRNAs, and 49 mRNAs critical in GRE development.
- Validated elevated expression of GABARAPL1, GRAMD1B, and IQSEC3 in the GRE group.
- Constructed a significant lncRNA-microRNA-Gene regulatory network and implicated ECM receptor interaction and long-term potentiation pathways.
Conclusions:
- The study provides a comprehensive molecular profile of GRE.
- Findings offer novel perspectives on GRE-induced brain network changes and identify potential therapeutic avenues.
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