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Profiling Analysis of Circular RNA and mRNA in Human Temporal Lobe Epilepsy with Hippocampal Sclerosis ILAE Type 1

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Abstract

Hippocampal sclerosis (HS) is the most common surgical pathology associated with temporal lobe epilepsy (TLE). However, the cause of TLE with or without HS remains unknown. Our current study aimed to illustrate the essential molecular mechanism that is potentially involved in the pathogenesis of TLE-HS and to shed light on the transcriptional changes associated with hippocampal sclerosis. Compared to no-HS group, 341 mRNA transcripts and 131 circRNA transcripts were differentially expressed in ILAE type 1 group. The raw sequencing data have been deposited into sequence-read archive (SRA) database under accession number PRJNA699348.Gene Ontology analysis demonstrated that the dysregulated genes were associated with the biological processes of vesicle-mediated transport. Enrichment analysis demonstrated that dysregulated genes were involved mainly in the MAPK signal pathway. Subsequently, A total of 441 known or predicted interactions were formed among DEGs, and the most important module was detected in the PPI network using the MCODE plug-in. There were mainly four functional modules enriched: ER to Golgi transport vesicle membrane, Basal transcription factors, GABA-gated chloride ion channel activity, CENP-A containing nucleosome assembly. A circRNA-mRNA co-expression network was constructed including 5 circRNAs(hsa_circ_0025349, hsa_circ_0002405, hsa_circ_0004805, hsa_circ_0032254, and hsa_circ_0032875) and three mRNAs (FYN, SELENBP1, and GRIPAP1) based on the normalized mRNA signal intensities. This is the first to report the circRNAs and mRNAs expression profile of surgically resected hippocampal tissues from TLE patients of ILAE-1 and no-HS, and these results may provide new insight into the transcriptional changes associated with this pathology.

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Abbreviations

TLE:

Temporal lobe epilepsy

HS:

Hippocampal sclerosis

ILAE:

International league against epilepsy

AEDs:

Antiepileptic drugs

RT-PCR:

Reverse transcription polymerase chain reaction

circRNA:

Circular RNA

DEGs:

Different expression genes

GO:

Gene ontology

KEGG:

Kyoto encyclopedia of genes and genomes

MAPK:

Mitogen-activated protein kinase

PPI:

Protein–protein interaction

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Acknowledgements

This work was supported by the National Nature Science Foundation of China (No:U20A20383; No. 8172678; No. 82002644; No. 81802755) and Harbin Medical University First Hospital Scientific Research Innovation Fund (No. 2020L06).

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Correspondence to Haiyang Wang or Zhiguo Lin.

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All procedures performed in this study involving human participants were in accordance with the ethical standards of the First Clinical College Ethics Committee of Harbin Medical University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For minors/children less than 16 years enrolled in our study, we obtained written informed consent from the parents.

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Informed consent was obtained from all individual participants included in this study.

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Gene bank: The raw sequencing data have been deposited into sequence read archive (SRA) database under accession number PRJNA699348.

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Gu, Y., Wu, H., Wang, T. et al. Profiling Analysis of Circular RNA and mRNA in Human Temporal Lobe Epilepsy with Hippocampal Sclerosis ILAE Type 1. Cell Mol Neurobiol 42, 2745–2755 (2022). https://doi.org/10.1007/s10571-021-01136-w

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