Construction and analysis of a dysregulated lncRNA-associated ceRNA network in a rat model of temporal lobe epilepsy

Zhao Hui Luo; Alsharafi Walid A; Yuanyuan Xie; Hongyu Long; Wenbiao Xiao; Liqun Xu; Yujiao Fu; Li Feng; Bo Xiao

doi:10.1016/j.seizure.2019.04.010

Construction and analysis of a dysregulated lncRNA-associated ceRNA network in a rat model of temporal lobe epilepsy

Seizure. 2019 Jul:69:105-114. doi: 10.1016/j.seizure.2019.04.010. Epub 2019 Apr 15.

Authors

Zhao Hui Luo¹, Alsharafi Walid A¹, Yuanyuan Xie¹, Hongyu Long¹, Wenbiao Xiao¹, Liqun Xu¹, Yujiao Fu¹, Li Feng², Bo Xiao³

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, PR China; Neurology Institute of Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
² Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, PR China; Neurology Institute of Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China. Electronic address: fenglihx@163.com.
³ Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, PR China; Neurology Institute of Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China. Electronic address: xiaobo_xy@126.com.

PMID: 31005697
DOI: 10.1016/j.seizure.2019.04.010

Abstract

Purpose: The aim of this work was to investigate expression and cross-talk between long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) in a rat model of temporal lobe epilepsy (TLE).

Methods: Noncoding RNA chips were used to explore the expression and relationship between lncRNAs and miRNAs in a rat model of TLE. The expression of different lncRNAs and mRNAs was analysed by Pearson's correlation coefficient, and the function of each lncRNA was annotated by co-expressed genes based on gene ontology classification using DAVID. MiRNA-lncRNA interactions were predicted by using StarBase v2.0, and the competing endogenous RNA (ceRNA) relationship between lncRNAs and miRNAs was built by using Cytoscape software. Real-time PCR was used to verify chip results.

Results: According to the expression profile analysis, 54 lncRNAs, 36 miRNAs and 122 mRNAs were dysregulated in TLE rat model compared to normal controls. The functions of lncRNAs in epilepsy were annotated by their co-expressed genes based on the "guilt by association" strategy. DAVID analysis revealed that differentially expressed lncRNA functions were involved in "potassium channel activity", "metal ion transmembrane transporter activity", and "voltage-gated potassium channel activity". Based on the ceRNA theory, 13 mRNAs, 10 miRNAs and 11 lncRNAs comprise the lncRNA-miRNA-mRNA ceRNA relationship in epilepsy.

Conclusions: The molecular functions of the differentially expressed genes play an important role in the pathogenesis of voltage-gated potassium channel activity. Further ceRNA analyses suggest that modulation of lncRNAs could emerge as a promising therapeutic target for TLE.

Keywords: Competing endogenous RNA (ceRNA); DAVID; Long non-coding RNAs (lncRNAs); Pathway; Temporal lobe epilepsy (TLE); microRNAs (miRNAs).

MeSH terms

Animals
Disease Models, Animal
Epilepsy, Temporal Lobe / genetics*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Gene Ontology
Male
MicroRNAs / genetics
Oligonucleotide Array Sequence Analysis
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism*
Rats, Sprague-Dawley

Substances

MicroRNAs
RNA, Long Noncoding