Academic Journal
Integrative network analysis of miRNA-mRNA expression profiles during epileptogenesis in rats reveals therapeutic targets after emergence of first spontaneous seizure
| Title: | Integrative network analysis of miRNA-mRNA expression profiles during epileptogenesis in rats reveals therapeutic targets after emergence of first spontaneous seizure |
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| Authors: | Niraj Khemka, Gareth Morris, Laleh Kazemzadeh, Lara S. Costard, Valentin Neubert, Sebastian Bauer, Felix Rosenow, Morten T. Venø, Jørgen Kjems, David C. Henshall, Jochen H. M. Prehn, Niamh M. C. Connolly |
| Source: | Scientific Reports, Vol 14, Iss 1, Pp 1-16 (2024) |
| Publisher Information: | Nature Portfolio, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Epilepsy, Epileptogensis, microRNA, miRNA-mRNA interactions, Bayesian modelling, Temporal expression profiling, Medicine, Science |
| More Details: | Abstract Epileptogenesis is the process by which a normal brain becomes hyperexcitable and capable of generating spontaneous recurrent seizures. The extensive dysregulation of gene expression associated with epileptogenesis is shaped, in part, by microRNAs (miRNAs) – short, non-coding RNAs that negatively regulate protein levels. Functional miRNA-mediated regulation can, however, be difficult to elucidate due to the complexity of miRNA-mRNA interactions. Here, we integrated miRNA and mRNA expression profiles sampled over multiple time-points during and after epileptogenesis in rats, and applied bi-clustering and Bayesian modelling to construct temporal miRNA-mRNA-mRNA interaction networks. Network analysis and enrichment of network inference with sequence- and human disease-specific information identified key regulatory miRNAs with the strongest influence on the mRNA landscape, and miRNA-mRNA interactions closely associated with epileptogenesis and subsequent epilepsy. Our findings underscore the complexity of miRNA-mRNA regulation, can be used to prioritise miRNA targets in specific systems, and offer insights into key regulatory processes in epileptogenesis with therapeutic potential for further investigation. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-66117-7 |
| Access URL: | https://doaj.org/article/aec36402be9d4848857dd99eb744d751 |
| Accession Number: | edsdoj.36402be9d4848857dd99eb744d751 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-024-66117-7 |
| Published in: | Scientific Reports |
| Language: | English |