Reduced Mature MicroRNA Levels in Association with Dicer Loss in Human Temporal Lobe Epilepsy with Hippocampal Sclerosis

McKiernan, Ross C.; Jiménez-Mateos, Eva M.; Bray, Isabella; Engel, Tobías; Brennan, Gary P.; Sano, Takanori; Michalak, Zuzanna; Moran, Catherine; Delanty, Norman; Farrell, Michael; O’Brien, Donncha F.; Meller, Robert; Simon, Roger P.; Stallings, Raymond L.; Henshall, David C.

doi:10.1371/journal.pone.0035921

Cited by 116 publications

(105 citation statements)

References 55 publications

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“…DROSHA is a double-stranded RNA-specific endoribonuclease that influences the initial step of miRNA biogenesis [43], the loss of which causes neuronal and glial abnormality, seizures, and neurodegenerative disorders [44]. McKiernan and colleagues found that reduced ribonuclease III levels in TLE patients might influence the epileptic phenotype [45]. Our study indicated that circ-EFCAB2 and circ-DROSHA might be involved in the process of TLE by regulating EFCAB2 and DROSHA (Fig.…”

Section: Discussionmentioning

confidence: 71%

High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy

Lin

Sun

et al. 2018

Cell Physiol Biochem

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Background/Aims: Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. Methods: Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients. Total RNA was isolated, and high-throughput sequencing was used to profile the transcriptome of dysregulated circRNAs. Quantitative PCR was performed for the validation of changed circRNAs. Results: In total, 78983 circRNAs, including 15.29% known and 84.71% novel circRNAs, were detected in this study. Intriguingly, 442 circRNAs were differentially expressed between the TLE and non-TLE groups (fold change≥2.0 and FDR≤0.05). Of these circRNAs, 188 were up-regulated, and 254 were down-regulated in the TLE patient group. Eight circRNAs were validated by real-time PCR. Remarkably, circ-EFCAB2 was intensely up-regulated, while circ-DROSHA expression was significantly lower in the TLE group than in the non-TLE group (P<0.05). Bioinformatic analysis revealed that circ-EFCAB2 binds to miR-485-5p to increase the expression level of the ion channel CLCN6, while circ-DROSHA interacts with miR-1252-5p to decrease the expression level of ATP1A2. Conclusions: The dysregulations of circRNAs may reflect the pathogenesis of TLE and circ-EFCAB2 and circ-DROSHA might be potential therapeutic targets and biomarkers in TLE patients.

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Section: Discussionmentioning

confidence: 71%

High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy

Lin

Sun

et al. 2018

Cell Physiol Biochem

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“…Selective reduction in Dicer levels in tissue from TLE patients with severe hippocampal sclerosis (HS), suggested that Dicer loss may contribute to the pathogenesis of TLE-HS [26]. MiR-184 has been identified as a seizure-regulated miRNA and its inhibition increases neuronal death after seizures [27].…”

Section: Discussionmentioning

confidence: 99%

microRNA s (9, 138, 181A, 221, and 222) and mesial temporal lobe epilepsy in developing brains

Ashhab

Omran²,

Kong

et al. 2013

Translational Neuroscience

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Background: Recently, microRNAs (miRNAs) have attracted much attention as novel players in the pathogenesis of mesial temporal lobe epilepsy (MTLE) in mature and developing brains. This study aimed to investigate the expression dynamics of miR-9, miR-138, miR-181a, miR-221, and miR-222 in the hippocampus of an immature rat model during the three stages of MTLE development and in children with MTLE. Methodology: qPCR was used to measure expression levels during the three stages of MTLE development (2 h, 3, and 8 weeks after induction of lithium-pilocarpine status epilepticus, representing the acute, latent, and chronic stages, respectively. Expression levels were also measured in hippocampi obtained from children with MTLE and normal controls. Results: In the rat model, miR-9 was significantly upregulated during the acute and chronic stages relative to controls, but not during the latent stage. MiR-138, miR-221 and miR-222 were all downregulated during all three stages of MTLE development. MiR-181a was downregulated during the acute stage, upregulated during the chronic stage, and unaltered during the latent stage. In children, miR-9 and miR-181a were upregulated, while miR-138, miR-221, and miR-222 were downregulated. Conclusion: Modulation of these miRNAs may be a new strategy in designing antiepileptic and anticonvulsant therapies for the developing brain.

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“…Profiling studies were recently reported using resected hippocampus from temporal lobe epilepsy (TLE) patients [29•-30] along with work on individual miRNAs in human epilepsy 22-26••]. Significant changes were found for just under 100 different miRNAs and a number of the same miRNAs changed expression in the same direction as in the experimental work.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA and epilepsy

Henshall

2014

Current Opinion in Neurology

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113

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Purpose of Review To provide a synthesis of recent profiling studies investigating microRNA changes in experimental and human epilepsy and outline mechanistic, therapeutic and diagnostic potentials of this research area for clinical practice. Recent Findings A series of studies in experimental and human epilepsy have undertaken large-scale expression profiling of microRNAs, key regulatory molecules in cells controlling protein levels. Levels of over 100 different microRNAs were found to either increase or decrease in the hippocampus, of which more than 20 were identified in more than one study, including higher levels of miR-23a, miR-34a, miR-132 and miR-146a. Altered levels of enzymes involved in microRNA biogenesis and function, including Dicer and Argonaute 2, have also been found in epileptic brain tissue. Functional studies using oligonucleotide-based inhibitors support roles for microRNAs in the control of cell death, synaptic structure, inflammation and the immune response. Finally, data show brain injuries that precipitate epilepsy generate unique microRNA profiles in biofluids. Summary MicroRNA represents a potentially important mechanism controlling protein levels in epilepsy. As such, microRNAs might be targeted to prevent or disrupt epilepsy as well as serve as diagnostic biomarkers of epileptogenesis.

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Reduced Mature MicroRNA Levels in Association with Dicer Loss in Human Temporal Lobe Epilepsy with Hippocampal Sclerosis

Cited by 116 publications

References 55 publications

High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy

High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy

microRNA s (9, 138, 181A, 221, and 222) and mesial temporal lobe epilepsy in developing brains

MicroRNA and epilepsy

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