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Genome-Wide DNA Methylation Patterns Analysis of Noncoding RNAs in Temporal Lobe Epilepsy Patients

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Abstract

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy and frequently evolving drug resistance. Although there is growing consensus that noncoding ribonucleic acids (ncRNAs) are modulators of TLE, the knowledge about the deoxyribonucleic acid (DNA) methylation patterns of ncRNAs in TLE remains limited. In the current study, we constructed DNA methylation profiles from 30 TLE patients and 30 healthy controls for ncRNAs, primarily focusing on long ncRNAs (lncRNAs) and microRNAs (miRNAs), by reannotating data of DNA methylation BeadChip. Statistics analyses have revealed a global hypermethylation pattern in miRNA and lncRNA gene in TLE patients. Bioinformatic analyses have found aberrantly methylated miRNAs and lncRNAs are related to ion channel activity, drug metabolism, mitogen-activated protein kinase (MAPK) signaling pathway, and neurotrophin signaling pathway. Aberrantly methylated ncRNA and pathway target might be involved in TLE development and progression. The methylated and demethylated ncRNAs identified in this study provide novel insights for developing TLE biomarkers and potential therapeutic targets.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (NNSFC), grant no. 81401078 to H.Y.L and no. 81371435 to B.X.

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Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China

    Wenbiao Xiao, Hongyu Long, Zhaohui Luo, Shuyu Li, Na Deng & Bo Xiao

  2. Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150081, China

    Yuze Cao, Jianjian Wang, Xiaoyan Lu, Tianfeng Wang & Lihua Wang

  3. Department of Neurology, Peking Union Medical College Hospital, Beijing, 100032, China

    Yuze Cao

  4. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China

    Shangwei Ning

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  1. Wenbiao Xiao
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  2. Yuze Cao
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  3. Hongyu Long
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  4. Zhaohui Luo
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Correspondence to Shangwei Ning, Lihua Wang or Bo Xiao.

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Wenbiao Xiao and Yuze Cao contributed equally to this work.

Electronic Supplementary Material

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Fig. S1

Detail information about clinical subgroups of TLE. a Bar graphs illustrating the distribution of disease onset age and disease course for 30 TLE patients. Red bars represent disease course and blue bars for disease onset age. Red serial number represents drug-resistant patient, blue serial number for drug-responsive patient. b Pie graphs illustrating the rate distribution of detail antiepileptic drug for 30 TLE patients. c Pie graphs illustrating the rate distribution of monotherapy and combination drug therapy for 30 TLE patients. (GIF 177 kb)

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High resolution image (TIFF 24263 kb)

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Fig. S2

A depiction of MAPK pathway in KEGG database. The KEGG annotated MAPK pathway as significantly enriched for TLE. Proteins or complexes targeted by differentially methylated miRNAs or lncRNAs are indicated in red character. Two important genes (CACN and MEF2C) are target genes and meanwhile are reported implicated in epilepsy or seizure phenotype in PubMed database and are indicated in red character and yellow background. (GIF 75 kb)

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High resolution image (TIFF 9632 kb)

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Xiao, W., Cao, Y., Long, H. et al. Genome-Wide DNA Methylation Patterns Analysis of Noncoding RNAs in Temporal Lobe Epilepsy Patients. Mol Neurobiol 55, 793–803 (2018). https://doi.org/10.1007/s12035-016-0353-x

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