An SNP site in pri-miR-124, a brain expressed miRNA gene, no contribution to mesial temporal lobe epilepsy in an Italian sample

Manna, Ida; Labate, Angelo; Borzì, Giuseppe; Mumoli, Laura; Cavalli, Salvatore M.; Sturniolo, Miriam; Quattrone, Aldo; Gambardella, Antonio

doi:10.1007/s10072-016-2597-7

Cited by 15 publications

(9 citation statements)

References 16 publications

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“…LncRNAs not only stimulate or inhibit the expression of target genes by combining directly with the target gene, but also participate in the regulation of gene expression by participating in histone modification as well as the recruitment of transcription factors . In addition, lncRNAs can also be used as ceRNAs that are capable of interacting with miRNAs, which together participate in the expression of target genes, and play significant roles in the occurrence and development of various diseases . LncRNAs are involved in the expression regulation of certain important coding genes, helping to facilitate nervous system growth and development in a certain space and in a certain time sequence, in addition to participating in the functioning of the nervous system .…”

Section: Discussionmentioning

confidence: 99%

“…20 In addition, lncRNAs can also be used as ceRNAs that are capable of interacting with miRNAs, which together participate in the expression of target genes, and play significant roles in the occurrence and development of various diseases. 21 LncRNAs are involved in the expression regulation of certain important coding genes, helping to facilitate nervous system growth and development in a certain space and in a certain time sequence, in addition to participating in the functioning of the nervous system. 22 Recent studies have shown that specific lncRNA is closely related to neural cell differentiation, synapses, elevated neuronal excitability, and neural network connection and remodeling, suggesting that it may be involved in the occurrence and development of epilepsy.…”

Section: Discussionmentioning

confidence: 99%

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Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Zheng

et al. 2019

The Kaohsiung J of Med Scie

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Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR‐135a‐5p, as well as those between miR‐135a‐5p and 3′ untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual‐luciferase reporter gene assay. The expression of miR‐135a‐5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR‐135a‐5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv‐shGAS5 and Lv‐miR‐135a‐5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR‐135a‐5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR‐135a‐5p. After the treatment of Lv‐shGAS5 and Lv‐miR‐135a‐5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR‐135a‐5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Zheng

et al. 2019

The Kaohsiung J of Med Scie

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“…In some previous studies, it has also been reported that rs531564 was not associated with impulsiveness, 13 mesial temporal lobe epilepsy, or Alzheimer’s disease. 12 , 23 However, because of the limitation of sample size, false-negative results may occur, especially for the correlation between rs531564 and antidepressant response. Thus, these findings need to be validated in a larger sample.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the association of <em>MIR124-1</em> and its target gene <em>RGS4</em> polymorphisms with major depressive disorder and antidepressant response

Zeng¹,

Shen²,

Yu³

et al. 2018

NDT

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BackgroundIncreasing evidence has indicated that dysfunction of miR-124 and target gene regulator of G protein signaling 4 (RGS4) may be involved in the etiology and treatment of major depressive disorder (MDD). However, the molecular mechanisms are not fully understood. This study aimed to investigate whether common genetic variations in these two genes are associated with MDD and therapeutic response to antidepressants in the Chinese population.MethodsThree polymorphisms including rs531564 (a functional single-nucleotide polymorphism [SNP] in MIR124-1), rs10759 (a microRNA-binding site SNP in RGS4), and rs951436 (a promoter SNP in RGS4) were genotyped in 225 Chinese MDD patients and 436 controls. Among the MDD patients, 147 accepted antidepressant treatment for 8 weeks with therapeutic evaluation at baseline, week 2, week 4, week 6, and week 8 using the 17-item Hamilton Rating Scale for Depression. Multifactor dimensionality reduction (MDR) was used to identify gene–gene interactions.ResultsNo significant association with MDD was discovered in single-SNP analyses. However, by MDR analysis, the three-locus model of gene–gene interaction was the best for predicting MDD risk. In pharmacogenetic study, a significant association was found in genotypic frequencies of rs951436 between the remitter and non-remitter groups (p=0.026, correction p=0.078). For further analysis, the rs951436 heterozygote carriers had threefold probabilities of achieving clinical complete remission (odds ratio =3.00, 95% confidence interval =1.33–6.76, p=0.007, correction p=0.021) as compared with rs951436 homozygotes (AA+CC) after 8 weeks of treatment.ConclusionAn interaction effect of MIR124-1 and RGS4 polymorphisms may play a more important role than individual factors for MDD development. Moreover, RGS4 gene polymorphisms may be associated with antidepressant response among the Han population.

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“…A number of candidate gene association studies have now been reported but there is no compelling evidence yet that genetic epilepsies are caused by mutations or variation in miRNA genes. [52][53][54][55] There has been no systematic effort to examine the contribution of miRNA sequence variation to human epilepsy. This is about to change.…”

Section: Genetic Variation In Mirnasmentioning

confidence: 99%

MicroRNAs in epilepsy: pathophysiology and clinical utility

Henshall

Hamer

Pasterkamp

et al. 2016

The Lancet Neurology

208

187

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In the past 5 years, studies have found changes in miRNA levels in the hippocampus of patients with temporal lobe epilepsy and in neural tissues from animal models of epilepsy. Early functional studies showed that silencing of brain-specific miR-134 using antisense oligonucleotides (antagomirs) had potent antiseizure effects in animal models, whereas genetic deletion of miR-128 produced fatal epilepsy in mice. Levels of certain miRNAs were also found to be altered in the blood of rodents after seizures. In the past 18 months, functional studies have identified nine novel miRNAs that appear to influence seizures or hippocampal pathology. Their targets include transcription factors, neurotransmitter signalling components, and modulators of neuroinflammation. New approaches to manipulate miRNAs have been tested, including injection of mimics (agomirs) to enhance brain levels of miRNAs. Altered miRNA expression has also been reported in other types of refractory epilepsy and our understanding of how miRNA levels are controlled has grown, with studies on DNA methylation indicating epigenetic regulation. Biofluids (blood) of patients with epilepsy have shown differences in quantity of circulating miRNAs, implying diagnostic biomarker potential. WHERE NEXT?: Recent functional studies need to be replicated to build a robust evidence base. The specific cell types in which miRNAs execute their functions and their primary targets have to be identified, to fully explain the phenotypic effects of modulating miRNAs. Delivery of large molecules such as antisense inhibitors or mimics to the brain poses a challenge, and the multi-targeting effects of miRNAs create additional risks of unanticipated side effects. Potential genetic variation in miRNAs should be explored as the basis for disease susceptibility. The latest findings provide a rich source of new miRNA targets, but substantial challenges remain before their role in the pathogenesis, diagnosis, and treatment of epilepsy can be translated into clinical practice.

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An SNP site in pri-miR-124, a brain expressed miRNA gene, no contribution to mesial temporal lobe epilepsy in an Italian sample

Cited by 15 publications

References 16 publications

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Analysis of the association of <em>MIR124-1</em> and its target gene <em>RGS4</em> polymorphisms with major depressive disorder and antidepressant response

MicroRNAs in epilepsy: pathophysiology and clinical utility

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