Expression levels of microRNA-199 and hypoxia-inducible factor-1 alpha in brain tissue of patients with intractable epilepsy

Jiang, Guohui; Zhou, Ruijiao; He, Xuefeng; Shi, Zhiqing; Huang, Min; Yu, Jiang; Wang, Xiaoming

doi:10.3109/00207454.2014.994209

Cited by 36 publications

(26 citation statements)

References 33 publications

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“…A previous study has reported that some neuronal miRNA may show context-dependent roles in neurological diseases through regulating the spatial and temporal expression levels of protein-coding genes, such as miR199b [10]. miR199b can high-risk and low-risk patients, respectively.…”

Section: Discussionmentioning

confidence: 99%

Five miRNAs considered as molecular targets for predicting neuroglioma

Yang

Wang

2015

Tumor Biol.

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Neuroglioma is a complex neuroglial tumor involving dysregulation of many biological pathways at multiple levels. Here, we aim to screen differentially expressed miRNAs (DEMs) as well as the functions and pathways of their target genes in neuroglioma. miRNA high-throughput sequencing data were downloaded from The Cancer Genome Atlas (TCGA), and then the DEMs were subjected to perform principal component analysis (PCA) based on their expression values. Following that, Targetscan software was used to predict the target genes, and enrichment analysis and pathway annotation of these target genes were done by DAVID and KEGG, respectively. Finally, survival analysis between the DEMs and patients' survival time was done, and the miRNAs with prediction potential were obtained. A total of 33 DEMs were obtained, among which 25 miRNAs were upregulated including hsa-mir-675, hsa-mir-196a-1, and hsa-mir-196a-2, while eight miRNAs were downregulated including hsa-mir-1911, hsa-mir-1264, and hsa-mir-1298. Five miRNAs with diagnostic and preventive potentials were significantly correlated with survival time, including has-mir-155, has-mir-199b, has-mi-10a, has-mir-1274b, and has-mir-455. The target genes of miRNA identified in this study played important roles in tumor signaling pathways, and their detailed functions could be further studied so as to explore novel neuroglioma therapies.

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Section: Discussionmentioning

confidence: 99%

Five miRNAs considered as molecular targets for predicting neuroglioma

Yang

Wang

2015

Tumor Biol.

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“…The deceased great paternal grandfather of the proband (not tested for THAP1 mutations) probably suffered from writer’s cramp. For more specific information about the patient and his family history see our previous report [10]. …”

Section: Resultsmentioning

confidence: 99%

“…The Glu56 forms part of the H2 helix, which is involved in the zinc-binding domain formation. The Glu56Gly mutation has already been described in our previous paper, for more discussion see [10]. The Ile80 is located in the H4 helix in the C-terminal region of the THAP domain and belongs to the highly conserved AVPTIF motif, encompassing amino acids 76–81 [1].…”

Section: Discussionmentioning

confidence: 99%

“…THAP1 exons 1, 2 and 3 including exon-intron boundaries and 5’UTR fragment were PCR-amplified and sequenced as described elsewhere [10]. The presence of the identified mutations was additionally confirmed with PCR-RFLP method with the use of Hpy188I, New England BioLabs (Glu56Gly); SspI, Thermo Scientific (Ile80Val); and BccI, New England Biolabs (-249C>A) restriction enzymes.…”

Section: Methodsmentioning

confidence: 99%

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Screening for THAP1 Mutations in Polish Patients with Dystonia Shows Known and Novel Substitutions

et al. 2015

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The aim of this study was to assess the presence of DYT6 mutations in Polish patients with isolated dystonia and to characterize their phenotype. We sequenced THAP1 exons 1, 2 and 3 including exon-intron boundaries and 5’UTR fragment in 96 non-DYT1 dystonia patients. In four individuals single nucleotide variations were identified. The coding substitutions were: c. 238A>G (p.Ile80Val), found in two patients, and c.167A>G (p.Glu56Gly), found in one patient. The same variations were present also in the patients’ symptomatic as well as asymptomatic relatives. Mutation penetration in the analyzed families was 50-66.7%. In the fourth patient, a novel c.-249C>A substitution in the promoter region was identified. The patient, initially suspected of idiopathic isolated dystonia, finally presented with pantothenate kinase 2-associated neurodegeneration phenotype and was a carrier of two PANK2 mutations. This is the first identified NBIA1 case carrying mutations in both PANK2 and THAP1 genes. In all symptomatic THAP1 mutation carriers (four probands and their three affected relatives) the first signs of dystonia occurred before the age of 23. A primary localization typical for DYT6 dystonia was observed in six individuals. Five subjects developed the first signs of dystonia in the upper limb. In one patient the disease began from laryngeal involvement. An uncommon primary involvement of lower limb was noted in the THAP1 and PANK2 mutations carrier. Neither of these THAP1 substitutions were found in 150 unrelated healthy controls. To the contrary, we identified a heterozygous C/T genotype of c.57C>T single nucleotide variation (p.Pro19Pro, rs146087734) in one healthy control, but in none of the patients. Therefore, a previously proposed association between this substitution and DYT6 dystonia seems unlikely. We found also no significant difference between cases and controls in genotypes distribution of the two-nucleotide -237-236 GA>TT (rs370983900 & rs1844977763) polymorphism.

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“…MiR‐199b, which is located on chromosome 9q34.11, has been widely researched in recent years and implicated in tumour progression in tumours such as myeloid leukaemia , lymphoid leukaemia , medulloblastoma , choriocarcinoma , endometrioid endometrial carcinoma , ovarian cancer , breast cancer , prostate cancer , hepatocellular carcinoma , colorectal cancer , Kaposi's sarcoma , osteosarcoma and Ewing's sarcoma . Additionally, miR‐199b has also been implicated in other pathologies such as heart failure , idiopathic pulmonary arterial hypertension and intractable epilepsy . Furthermore, in a recent integrated microRNA–mRNA study, miR‐199b‐5p was found to be one of the top 10 down‐regulated miRNAs in OPLL cells compared to the normal posterior longitudinal ligament cells , thus suggesting that miR‐199b‐5p may be involved in the process of ligament ossification.…”

Section: Discussionmentioning

confidence: 99%

MiR‐199b‐5p inhibits osteogenic differentiation in ligamentum flavum cells by targeting JAG1 and modulating the Notch signalling pathway

Chen

Fan

et al. 2016

J Cellular Molecular Medi

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Ossification of the ligamentum flavum (OLF) is a pathology almost only reported in East Asian countries. The leading cause of OLF is thoracic spinal canal stenosis and myelopathy. In this study, the role of miR‐199b‐5p and jagged 1 (JAG1) in primary ligamentum flavum cell osteogenesis was examined. MiR‐199b‐5p was found to be down‐regulated during osteogenic differentiation in ligamentum flavum cells, while miR‐199b‐5p overexpression inhibited osteogenic differentiation. In addition, JAG1 was found to be up‐regulated during osteogenic differentiation in ligamentum flavum cells, while JAG1 knockdown via RNA interference caused an inhibition of Notch signalling and osteogenic differentiation. Moreover, target prediction analysis and dual luciferase reporter assays supported the notion that JAG1 was a direct target of miR‐199b‐5p, with miR‐199b‐5p found to down‐regulate both JAG1 and Notch. Further, JAG1 knockdown was demonstrated to block the effect of miR‐199b‐5p inhibition. These findings imply that miR‐199b‐5p performs an inhibitory role in osteogenic differentiation in ligamentum flavum cells by potentially targeting JAG1 and influencing the Notch signalling pathway.

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Expression levels of microRNA-199 and hypoxia-inducible factor-1 alpha in brain tissue of patients with intractable epilepsy

Abstract: These data suggest that the abnormal expression of miR-199 and HIF-1α in epileptic brain tissue may be involved in the pathophysiology of human epilepsy and that the expression of HIF-1α may be regulated by miR-199. These findings may provide new insights into the treatment of epilepsy.

Cited by 36 publications

References 33 publications

Five miRNAs considered as molecular targets for predicting neuroglioma

Five miRNAs considered as molecular targets for predicting neuroglioma

Screening for THAP1 Mutations in Polish Patients with Dystonia Shows Known and Novel Substitutions

MiR‐199b‐5p inhibits osteogenic differentiation in ligamentum flavum cells by targeting JAG1 and modulating the Notch signalling pathway

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