Identification of microRNA signature in different pediatric brain tumors

Tantawy, M.; Elzayat, Mariam G; Yehia, Dina; Taha, Hala

doi:10.1590/1678-4685-gmb-2016-0334

Cited by 31 publications

(27 citation statements)

References 37 publications

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“…Braoudaki et al (2014) used a microRNA (miRNA) signature to predict the clinical outcome in pediatric CNS tumors, but only 34 medulloblastomas were analyzed with other brain tumors, identifying only two signature miRNAs, which were not used to construct predictive models. Tantawy et al (2018) also investigated miRNA signature for medulloblastoma; however, only a total of 82 miRNAs were assessed, in a cohort of 30 medulloblastoma cases with another 90 pediatric brain tumors, resulting in only 1 miRNA that was specific to medulloblastoma. The prognostic model established by Tamayo et al (2011) was the only model we found, that could be used to predict clinical outcomes based on expression profiles.…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of a 13-Gene Signature for Prognosis Prediction in Medulloblastoma

et al. 2020

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Background: Recent studies have identified several molecular subgroups of medulloblastoma associated with distinct clinical outcomes; however, no robust gene signature has been established for prognosis prediction. Our objective was to construct a robust gene signature-based model to predict the prognosis of patients with medulloblastoma. Methods: Expression data of medulloblastomas were acquired from the Gene Expression Omnibus (GSE85217, n = 763; GSE37418, n = 76). To identify genes associated with overall survival (OS), we performed univariate survival analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. A risk score model was constructed based on selected genes and was validated using multiple datasets. Differentially expressed genes (DEGs) between the risk groups were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interaction (PPI) analyses were performed. Network modules and hub genes were identified using Cytoscape. Furthermore, tumor microenvironment (TME) was evaluated using ESTIMATE algorithm. Tumor-infiltrating immune cells (TIICs) were inferred using CIBERSORTx. Results: A 13-gene model was constructed and validated. Patients classified as high-risk group had significantly worse OS than those as low-risk group (Training set: p < 0.0001; Validation set 1: p < 0.0001; Validation set 2: p = 0.00052). The area under the curve (AUC) of the receiver operating characteristic (ROC) analysis indicated a good performance in predicting 1-, 3-, and 5-year OS in all datasets. Multivariate analysis integrating clinical factors demonstrated that the risk score was an independent predictor for the OS (validation set 1: p = 0.001, validation set 2: p = 0.004). We then identified 265 DEGs between risk groups and PPI analysis predicted modules that were highly related to central nervous system and embryonic development. The risk score was significantly correlated with programmed deathligand 1 (PD-L1) expression (p < 0.001), as well as immune score (p = 0.035), stromal score (p = 0.010), and tumor purity (p = 0.010) in Group 4 medulloblastomas. Correlations between the 13-gene signature and the TIICs in Sonic hedgehog and Group 4 medulloblastomas were revealed.

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Section: Discussionmentioning

confidence: 99%

Construction and Validation of a 13-Gene Signature for Prognosis Prediction in Medulloblastoma

et al. 2020

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“…Among the downregulated hits, we found a profound decrease (-11 fold) in the expression of miR-26a-2, which has been extensively studied in gliomas. From a neurodevelopmental perspective, downregulation of miR-26a-2 has been linked to impaired long-term potentiation and spine dynamics [64] as well as the proliferation of pediatric brain tumors [71]. Another study showed its downregulation in the hippocampus of peripubertal rats exposed to binge ethanol exposure [72], suggesting that these PNO offspring are possibly prone to alcohol addiction later in development.…”

Section: Discussionmentioning

confidence: 99%

Brain-Derived Extracellular Vesicle microRNA Signatures Associated with In Utero and Postnatal Oxycodone Exposure

Shahjin

Guda

Schaal

et al. 2019

Cells

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Oxycodone (oxy) is a semi-synthetic opioid commonly used as a pain medication that is also a widely abused prescription drug. While very limited studies have examined the effect of in utero oxy (IUO) exposure on neurodevelopment, a significant gap in knowledge is the effect of IUO compared with postnatal oxy (PNO) exposure on synaptogenesis-a key process in the formation of synapses during brain development-in the exposed offspring. One relatively unexplored form of cell-cell communication associated with brain development in response to IUO and PNO exposure are extracellular vesicles (EVs). EVs are membrane-bound vesicles that serve as carriers of cargo, such as microRNAs (miRNAs). Using RNA-Seq analysis, we identified distinct brain-derived extracellular vesicle (BDEs) miRNA signatures associated with IUO and PNO exposure, including their gene targets, regulating key functional pathways associated with brain development to be more impacted in the IUO offspring. Further treatment of primary 14-day in vitro (DIV) neurons with IUO BDEs caused a significant reduction in spine density compared to treatment with BDEs from PNO and saline groups. In summary, our studies identified for the first time, key BDE miRNA signatures in IUO-and PNO-exposed offspring, which could impact their brain development as well as synaptic function.Cells 2020, 9, 21 2 of 18 lack of studies that have compared the effect of in utero oxy (IUO) and postnatal oxy (PNO) exposure on synaptogenesis-a key process of the formation of synapses during brain development-in the exposed offspring. Synapses are key communication points between neurons, which play a critical role in the regulation of neurotransmission and brain plasticity [6].One relatively unexplored form of cell-cell communication associated with brain development in response to IUO and PNO exposure is extracellular vesicles (EVs) [7][8][9]. These membrane-bound vesicles, comprised of exosomes and microvesicles, originate from the multivesicular bodies and plasma membrane, respectively. Furthermore, these EVs, which carry a repertoire of cargo, including microRNAs (miRNAs), are shown to induce inflammation and subsequent neuronal damage, thus serving as key mediators of pathogenesis in several neurological and neurodegenerative disorders [10,11]. The main objective of this study was to identify differentially expressed BDEs miRNAs using RNA sequencing (RNA-Seq) and evaluate their impact on synaptic architecture during a key stage of brain development.

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“…O miR-27a encontra-se também superexpresso em glioma de baixo grau, sendo identificado nas diferentes linhas celulares de glioma (Ge et al, 2013;Tantawy et al, 2018;YANG et al, 2012), promovendo a proliferação de células de glioma via segmentação MXI1 regulando-o sinergicamente (XU et al, 2013). Foi demonstrado que o miR-27a pode estar envolvido na progressão do glioma através da junção de células aderentes, adesão focal, via de sinalização da neurotrofina, interações entre receptores de citocinas e citocinas, vias de sinalização MAPK, TGFβ, p53 e apoptótica, entre outras (YANG et al, 2012).…”

Section: Discussionunclassified

“…Identificada a superexpressão de miR-27a em glioma de baixo grau (Tantawy, Elzayat, Yehia, & Taha, 2018 A expressão lentiviral do anti-miR-27a é uma abordagem viável para a supressão de fenótipos malignos de células de glioma (FENG et al, 2012). (Cui, Li, Liu, & Cui, 2017).…”

Section: Mir-27a E Glioblastomaunclassified

Expressão dos microRNAs: miR-23a, miR-27a, miR-181b, miR-203 e miR-210 em neuroesferas e células aderidas de culturas de pacientes com glioblastoma

Aragón¹

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Identification of microRNA signature in different pediatric brain tumors

Cited by 31 publications

References 37 publications

Construction and Validation of a 13-Gene Signature for Prognosis Prediction in Medulloblastoma

Construction and Validation of a 13-Gene Signature for Prognosis Prediction in Medulloblastoma

Brain-Derived Extracellular Vesicle microRNA Signatures Associated with In Utero and Postnatal Oxycodone Exposure

Expressão dos microRNAs: miR-23a, miR-27a, miR-181b, miR-203 e miR-210 em neuroesferas e células aderidas de culturas de pacientes com glioblastoma

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