MicroRNA expression profile in epilepsy: breaking molecular barriers

Abstract

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules (21-24 nt) that negatively regulate gene expression, either by repression of translation or by degradation of messenger RNA. These molecules are involved in many important processes including cell differentiation, neurogenesis, formation of nervous system and others. Mesial temporal lobe epilepsy and epilepsy caused by cortical dysgenesis are among the leading causes of drug resistant epilepsy. OBJECTIVES: The objectives of this study were to characterize the expression profile of miRNAs and to investigate their regulation in mesial temporal lobe epilepsy (MTL) and in focal cortical dysplasias (FCDs). METHODS: Total RNA was extracted from hippocampal and neocortical tissue, maintained in paraffin or fresh-frozen, from patients who underwent surgery for seizure control. For comparison we used tissue obtained from autopsy. RNA was extracted and used in real time PCR reactions (157 miRNAs analyzed) or microarray chips (847 miRNAs analyzed). RESULTS: Bioinformatics analyzes identified three miRNAs with expression significantly different in patients with MTLE: let-7d, miR-29b and miR-30d; while in patients with FCDs we found 23 microRNAs differentially expressed. In addition, we found that different pathological forms of had different molecular signatures. CONCLUSIONS: The possible genes regulated by miRNAs with differential expression in tissue with mesial temporal sclerosis (MTS) are mainly related to neurogenesis and apoptosis. While in DCFs they were predominantly related to cell proliferation and migration. Our results demonstrate the importance of miRNA regulation the in molecular processes that lead to the lesions present in the MTS and the FCDs.

Genomic and Epigenetic Advances in Focal Cortical Dysplasia Types I and II: A Scoping Review

“…The dynamics of epigenetic processes, responsible for the regulation of normal brain activity, are gaining attention as possible dysregulated systems among different epilepsy etiologies (Hauser et al, 2018). DNA methylation and noncoding RNAs, such as microRNAs, are the two mechanisms implicated in the pathogenesis of FCD and influence phenotypic manifestations (Dogini et al, 2012;Lee et al, 2014;Li et al, 2016;Wang et al, 2016;Che et al, 2017;Avansini et al, 2018;Dixit et al, 2018;Kobow et al, 2019). These epigenetic mechanisms may function as molecular signatures for FCD subtypes, representing potential clinically useful biomarkers and drug targets (Dogini et al, 2012;Lee et al, 2014;Kobow et al, 2019).…”

“…DNA methylation and noncoding RNAs, such as microRNAs, are the two mechanisms implicated in the pathogenesis of FCD and influence phenotypic manifestations (Dogini et al, 2012;Lee et al, 2014;Li et al, 2016;Wang et al, 2016;Che et al, 2017;Avansini et al, 2018;Dixit et al, 2018;Kobow et al, 2019). These epigenetic mechanisms may function as molecular signatures for FCD subtypes, representing potential clinically useful biomarkers and drug targets (Dogini et al, 2012;Lee et al, 2014;Kobow et al, 2019). However, further studies are needed to confirm that these epigenetic patterns are specific for FCD and not shared with other entities in the MCD group.…”

“…Similar to DNA methylation profiles, microRNAs were differentially expressed between FCD subtypes, suggesting that distinct forms of FCD had different molecular signatures (Dogini et al, 2012;Lee et al, 2014). The heterogeneity of the patients in terms of pathological subtype, lesion location, and age is an important limitation of the microRNA expression profiling studies (Li et al, 2016).…”

“…Recent research has identified a possible role for microRNAs in the regulation of target genes in FCD. Several microRNAs, like miR-17∼92 cluster, hsa-miR-21, hsa-miR-155, hsa-miR-4521, miR-323a-5p, hsa-let-7f, has-miR-31, and hsa-miR-34a, have been reported to be differentially expressed in FCD type I and/or II compared with normal cortical tissue (Dogini et al, 2012;Lee et al, 2014;Wang et al, 2016;Che et al, 2017;Avansini et al, 2018).…”