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MicroRNA519d and microRNA4758 can identify gangliogliomas from dysembryoplastic neuroepithelial tumours and astrocytomas.

ABSTRACT: Glioneuronal tumours, including gangliogliomas and dysembryoplastic neuroepithelial tumours, represent the most common low-grade epilepsy-associated brain tumours and are a well-recognized cause of intractable focal epilepsy in children and young adults. Classification is predominantly based on histological features, which is difficult due to the broad histological spectrum of these tumours. The aim of the present study was to find molecular markers that can be used to identify entities within the histopathology spectrum of glioneuronal tumours. The focus of this study was on microRNAs (miRNAs). miRNAs are important post-transcriptional regulators of gene expression and are involved in the pathogenesis of different neurological diseases and oncogenesis. Using a miRNA array, miR-519d and miR-4758 were found to be upregulated in gangliogliomas (n=26) compared to control cortex (n=17), peritumoural tissue (n=7), dysembryoplastic neuroepithelial tumours (n=9) and astrocytomas (grade I-IV; subependymal giant cell astrocytomas, n=10; pilocytic astrocytoma, n=15; diffuse astrocytoma grade II, n=10; grade III, n=14 and glioblastoma n=15). Furthermore, the PI3K/AKT3/P21 pathway, which is predicated to be targeted by miR-519d and miR-4758, was deregulated in gangliogliomas. Functionally, overexpression of miR-519d in an astrocytic cell line resulted in a downregulation of CDKN1A (P21) and an increase in cell proliferation, whereas co-transfection with miR-4758 counteracted this effect. These results suggest that miR-519d and miR-4758 might work in concert as regulators of the cell cycle in low grade gliomas. Furthermore, these miRNAs could be used to distinguish gangliogliomas from dysembryoplastic neuroepithelial tumours and other low and high grade gliomas and may lead to more targeted therapy.

SUBMITTER: Bongaarts A

PROVIDER: S-EPMC6021349 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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MicroRNA519d and microRNA4758 can identify gangliogliomas from dysembryoplastic neuroepithelial tumours and astrocytomas.

Bongaarts Anika A Prabowo Avanita S AS Arena Andrea A Anink Jasper J JJ Reinten Roy J RJ Jansen Floor E FE Spliet Wim G M WGM Thom Maria M Coras Roland R Blümcke Ingmar I Kotulska Katarzyna K Jozwiak Sergiusz S Grajkowska Wieslawa W Söylemezoğlu Figen F Pimentel José J Schouten-van Meeteren Antoinette Y N AYN Mills James D JD Iyer Anand M AM van Vliet Erwin A EA Mühlebner Angelika A Aronica Eleonora E

Oncotarget 20180615 46

Glioneuronal tumours, including gangliogliomas and dysembryoplastic neuroepithelial tumours, represent the most common low-grade epilepsy-associated brain tumours and are a well-recognized cause of intractable focal epilepsy in children and young adults. Classification is predominantly based on histological features, which is difficult due to the broad histological spectrum of these tumours. The aim of the present study was to find molecular markers that can be used to identify entities within t ...[more]

PMID: 29963264

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Project description:Dysembryoplastic neuroepithelial tumors (DNTs) provide a unique model for studying the effects of seizures on cognitive development. Epilepsy and antiepileptic medications are prominent features in the lives and schooling of people who develop seizures in childhood. People with an adult onset share the same underlying brain pathology, but their childhood development is unaffected by seizures. Therefore, DNTs provide a model to examine the specific influence of seizures and their treatment on cognitive development, over and above the effects of the underlying pathology in epilepsy.We examined the neuropsychological characteristics of 56 adults with DNT and medically intractable epilepsy (mean age 32.7 years). Twenty-two adults (39%) had an age of onset of epilepsy before the age of 12 years (childhood-onset group). Scores on tests of intelligence (Verbal IQ and Performance IQ), reading, working memory, verbal learning, verbal recall, visual learning, and expressive and receptive language ability were analyzed.There were no significant localization effects (right vs. left vs. extratemporal) on any of the neuropsychological test scores. In the group as a whole, the neuropsychological test scores were significantly lower than healthy, age-matched controls on measures of Verbal IQ (p < 0.01), naming p < 0.01, verbal learning (p < 0.01), and working memory (p < 0.05). The childhood-onset group had significantly lower scores on the measures of Verbal IQ (p < 0.01), Performance IQ (p < 0.05), reading (p < 0.05), naming (p = 0.05), and verbal retention (p < 0.05) than those with an onset of seizures at the age of 12 or older.The traditional pattern of lateralized memory deficits seen in people with hippocampal sclerosis may not be present in people with temporal lobe epilepsy associated with a DNT. The presence of seizures and their treatment in early childhood may adversely influence the development of these core cognitive abilities, resulting in patterns of cognitive deficits that remain apparent in adulthood.

Dataset Information

MicroRNA519d and microRNA4758 can identify gangliogliomas from dysembryoplastic neuroepithelial tumours and astrocytomas.

Publications

MicroRNA519d and microRNA4758 can identify gangliogliomas from dysembryoplastic neuroepithelial tumours and astrocytomas.

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