miRNA signature in glioblastoma: Potential biomarkers and therapeutic targets

Rezaei, Omidvar; Honarmand, Kasra; Nateghinia, Saeedeh; Taheri, Mohammad; Ghafouri‐Fard, Soudeh

doi:10.1016/j.yexmp.2020.104550

Cited by 31 publications

(54 citation statements)

References 237 publications

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“…Some number of studies about miR-181a/b and miR-410 therapeutics have been carried out, and verified its tumor-suppressive role in gliomas. For instance, the expression of miR-181 family members has been decreased in glioma ( 11 ). While miR-181c has been the most down-regulated one in the WHO Grade I gliomas, miR-181a/b exhibited the fastest decrease rate, with a significant decrease in the glioblastoma ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

“…For instance, the expression of miR-181 family members has been decreased in glioma ( 11 ). While miR-181c has been the most down-regulated one in the WHO Grade I gliomas, miR-181a/b exhibited the fastest decrease rate, with a significant decrease in the glioblastoma ( 11 , 12 ). Forced up-regulation of miR-181a/b remarkably suppressed high-grade glioma cell lines (U87, TJ905, and U251) tumor growth, proliferation, invasion and promote tumor cells apoptosis ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

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Circulating miRNAs as Diagnostic and Prognostic Biomarkers in High-Grade Gliomas

Alzahrani

Beylerli³

et al. 2022

Front. Oncol.

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ObjectivesmiR-181a/b and miR-410 downregulation and miR-155 upregulation has been shown to play important roles in the oncogenesis and progression of gliomas including high-grade gliomas. However, the potential role of plasma miR-181a/b, miR-410 and miR-155 in the diagnosis and prognosis of high-grade gliomas remains poorly known.MethodsWe retrieved published articles from the PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science database and obtained different sets of data on microRNAs (miRNAs) expression profiling in glioma and highlighted the most frequently dysregulated miRNAs and their gene-targets (PDCD4, WNT5A, MET, and EGFR) in high-grade gliomas. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was carried out to measure the pre- and postoperative plasma levels of miR-181a/b, miR-410 and miR-155 in 114 Grade 3-4 glioma patients, 77 Grade 1-2 glioma patients and 85 healthy volunteers as control group. The diagnostic and prognostic value of circulating miR-181a/b, miR-410 and miR-155 as biomarker was estimated by the Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) and Kaplan–Meier analysis.ResultsWe found a plasma miRNA signature including three downexpressed miRNAs and one overexpressed (miR-181a, miR-181b and miR-410; miR-155) in high-grade glioma patients in comparison with low-grade glioma patients control group. The ROC curve AUC of these four circulating miRNAs were ≥ 0.75 for high-grade glioma patients in before and after surgery. Higher circulating miR-155 and lower miR-181a/b and miR-410 expression is associated with clinical data, clinic pathological variables, worse overall survival (OS) of patients and negative correlated with potential gene-targets expression. Moreover, Kaplan–Meier analysis showed that miR-181a/b, miR-410 and miR-155 were independent predictors of OS in high-grade glioma patients.ConclusionsOur data, for the first time, demonstrated that circulating miR-181a/b, miR-410 and miR-155 could be a useful diagnostic and prognostic non-invasive biomarkers in high-grade gliomas.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating miRNAs as Diagnostic and Prognostic Biomarkers in High-Grade Gliomas

Alzahrani

Beylerli³

et al. 2022

Front. Oncol.

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“…On the other hand, the actions of NRSF in gliomas involve microRNAs. These microRNAs include tumor-promoting miR-21, miR-10b, and miR26a, and tumor-inhibiting miR-326, miR-128, miR-181, miR-7, and miR-124a ( Fu et al, 2018 ; Huang et al, 2019 ; Bautista-Sánchez et al, 2020 ; Bhere et al, 2020 ; Rezaei et al, 2020 ; Stakaitis et al, 2020 ; Wang et al, 2020 ). For example, high NRSF expression in glioblastoma decreases the miR-124a expression, and thereby increasing the expression of NRSF-target genes, such as SNAI-1 (a transcription factor that promotes cell invasion and tumor metastases), Scp1, and PTPN12 (two small phosphatases), and finally stimulating cell proliferation ( Tivnan et al, 2014 ).…”

Section: Nrsf and Tumorigenesismentioning

confidence: 99%

Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System

Shen

Wang

et al. 2022

Front. Cell Dev. Biol.

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The neuron-restrictive silencer factor (NRSF), also known as repressor element 1 (RE-1) silencing transcription factor (REST) or X2 box repressor (XBR), is a zinc finger transcription factor that is widely expressed in neuronal and non-neuronal cells. It is a master regulator of the nervous system, and the function of NRSF is the basis of neuronal differentiation, diversity, plasticity, and survival. NRSF can bind to the neuron-restrictive silencer element (NRSE), recruit some co-repressors, and then inhibit transcription of NRSE downstream genes through epigenetic mechanisms. In neurogenesis, NRSF functions not only as a transcriptional silencer that can mediate the transcriptional inhibition of neuron-specific genes in non-neuronal cells and thus give neuron cells specificity, but also as a transcriptional activator to induce neuronal differentiation. Many studies have confirmed the association between NRSF and brain disorders, such as brain injury and neurodegenerative diseases. Overexpression, underexpression, or mutation may lead to neurological disorders. In tumorigenesis, NRSF functions as an oncogene in neuronal tumors, such as neuroblastomas, medulloblastomas, and pheochromocytomas, stimulating their proliferation, which results in poor prognosis. Additionally, NRSF-mediated selective targets gene repression plays an important role in the development and maintenance of neuropathic pain caused by nerve injury, cancer, and diabetes. At present, several compounds that target NRSF or its co-repressors, such as REST-VP16 and X5050, have been shown to be clinically effective against many brain diseases, such as seizures, implying that NRSF and its co-repressors may be potential and promising therapeutic targets for neural disorders. In the present review, we introduced the biological characteristics of NRSF; reviewed the progress to date in understanding the roles of NRSF in the pathophysiological processes of the nervous system, such as neurogenesis, brain disorders, neural tumorigenesis, and neuropathic pain; and suggested new therapeutic approaches to such brain diseases.

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“…These changes involve various aspects of GBM, including tumor initiation, aggressiveness, responses to drug treatments, and patient survival rates. Profiling and studying these miRNA expression differences can help to further classify GBM 7 – 10 . For example, based on miRNA and mRNA expression, five clinically and genetically distinct glioblastoma subclasses were classified, including oligoneural, radial glial, neural, neuromesenchymal, and astrocytic precursor glioblastoma 7 .…”

Section: Introductionmentioning

confidence: 99%

Machine learning and bioinformatics approaches for classification and clinical detection of bevacizumab responsive glioblastoma subtypes based on miRNA expression

Shi

2022

Sci Rep

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For the precise treatment of patients with glioblastoma multiforme (GBM), we classified and detected bevacizumab (BVZ)-responsive subtypes of GBM and found their differential expression (DE) of miRNAs and mRNAs, clinical characteristics, and related functional pathways. Based on miR-21 and miR-10b expression z-scores, approximately 30% of GBM patients were classified as having the GBM BVZ-responsive subtype. For this subtype, GBM patients had a significantly shorter survival time than other GBM patients (p = 0.014), and vascular endothelial growth factor A (VEGF) methylation was significantly lower than that in other GBM patients (p = 0.005). It also revealed 14 DE miRNAs and 7 DE mRNAs and revealed functional characteristics between GBM BVZ subgroups. After comparing several machine learning algorithms, the construction and cross-validation of the SVM classifier were performed. For clinical use, miR-197 was optimized and added to the miRNA panel for better classification. Afterwards, we validated the classifier with several GBM datasets and discovered some key related issues. According to this study, GBM BVZ subtypes can be classified and detected by a combination of SVM classifiers and miRNA panels in existing tissue GBM datasets. With certain modifications, the classifier may be used for the classification and detection of GBM BVZ subtypes for future clinical use.

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miRNA signature in glioblastoma: Potential biomarkers and therapeutic targets

Cited by 31 publications

References 237 publications

Circulating miRNAs as Diagnostic and Prognostic Biomarkers in High-Grade Gliomas

Circulating miRNAs as Diagnostic and Prognostic Biomarkers in High-Grade Gliomas

Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System

Machine learning and bioinformatics approaches for classification and clinical detection of bevacizumab responsive glioblastoma subtypes based on miRNA expression

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