Cerebrospinal fluid microRNAs as diagnostic biomarkers in brain tumors

2018 ◽  
Vol 56 (6) ◽  
pp. 869-879 ◽  
Author(s):  
Alena Kopkova ◽  
Jiri Sana ◽  
Pavel Fadrus ◽  
Ondrej Slaby
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumors ◽  
Communication Channel ◽  
Predictive Biomarkers ◽  
Waste Products ◽  
Diagnostic Biomarkers ◽  
Circulating Micrornas ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Extracellular Environment

Abstract Cerebrospinal fluid (CSF) is a body fluid that has many important functions and is in direct contact with the extracellular environment of the central nervous system (CNS). CSF serves as both the communication channel allowing the distribution of various substances among the CNS cells and the storage facility for the waste products these cells release. For these reasons, CSF is a potential source of diagnostic biomarkers of many CNS diseases, including brain tumors. Recent studies have revealed that CSF also contains circulating microRNAs (miRNAs), short non-coding RNAs that have been described as biomarkers in many cancers. However, CSF miRNAs are difficult to detect, which is why researchers face major challenges, including technological difficulties in its detection and its lack of standardization. Therefore, this review aims (i) to highlight the potential of CSF miRNAs as diagnostic, prognostic and predictive biomarkers in brain tumors, and (ii) to summarize technological approaches for detection of CSF miRNAs.

scholarly journals Evolving Landscape of Long Non-coding RNAs in Cerebrospinal Fluid: A Key Role From Diagnosis to Therapy in Brain Tumors

2021 ◽  
Vol 9 ◽  
Author(s):  
Kanghong Xu ◽  
Xinquan Jiang ◽  
Abakundana Nsenga Ariston Gabriel ◽  
Xiaomeng Li ◽  
Yunshan Wang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumors ◽  
Biological Fluid ◽  
Treatment Resistance ◽  
Molecular Fingerprints ◽  
Chromatin Dynamics ◽  
Biochemical Processes ◽  
Sequencing Technologies ◽  
The Central Nervous System ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are a type of non-coding RNAs that act as molecular fingerprints and modulators of many pathophysiological processes, particularly in cancer. Specifically, lncRNAs can be involved in the pathogenesis and progression of brain tumors, affecting stemness/differentiation, replication, invasion, survival, DNA damage response, and chromatin dynamics. Furthermore, the aberrations in the expressions of these transcripts can promote treatment resistance, leading to tumor recurrence. The development of next-generation sequencing technologies and the creation of lncRNA-specific microarrays have boosted the study of lncRNA etiology. Cerebrospinal fluid (CSF) directly mirrors the biological fluid of biochemical processes in the brain. It can be enriched for small molecules, peptides, or proteins released by the neurons of the central nervous system (CNS) or immune cells. Therefore, strategies that identify and target CSF lncRNAs may be attractive as early diagnostic and therapeutic options. In this review, we have reviewed the studies on CSF lncRNAs in the context of brain tumor pathogenesis and progression and discuss their potential as biomarkers and therapeutic targets.

scholarly journals Long non-coding RNAs in brain tumors

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Keisuke Katsushima ◽  
George Jallo ◽  
Charles G Eberhart ◽  
Ranjan J Perera
Keyword(s):  
Gene Expression ◽  
Brain Tumors ◽  
Brain Cancer ◽  
Regulation Of Gene Expression ◽  
Therapeutic Targets ◽  
Diagnostic Biomarkers ◽  
Cancer Pathogenesis ◽  
Current State ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.

scholarly journals Long Non-Coding RNAs and Related Molecular Pathways in the Pathogenesis of Epilepsy

2019 ◽  
Vol 20 (19) ◽  
pp. 4898 ◽  
Author(s):  
Villa ◽  
Lavitrano ◽  
Combi
Keyword(s):  
Biological Processes ◽  
Complete Understanding ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Diagnostic Biomarkers ◽  
Functional Roles ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Underlying Mechanisms ◽  
Coding Capacity

Epilepsy represents one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system (CNS). Recurrent seizures are the cardinal clinical manifestation. Although it has been reported that the underlying pathological processes include inflammation, changes in synaptic strength, apoptosis, and ion channels dysfunction, currently the pathogenesis of epilepsy is not yet completely understood. Long non-coding RNAs (lncRNAs), a class of long transcripts without protein-coding capacity, have emerged as regulatory molecules that are involved in a wide variety of biological processes. A growing number of studies reported that lncRNAs participate in the regulation of pathological processes of epilepsy and they are dysregulated during epileptogenesis. Moreover, an aberrant expression of lncRNAs linked to epilepsy has been observed both in patients and in animal models. In this review, we summarize latest advances concerning the mechanisms of action and the involvement of the most dysregulated lncRNAs in epilepsy. However, the functional roles of lncRNAs in the disease pathogenesis are still to be explored and we are only at the beginning. Additional studies are needed for the complete understanding of the underlying mechanisms and they would result in the use of lncRNAs as diagnostic biomarkers and novel therapeutic targets.

scholarly journals Targeted metabolomic profiling of cerebrospinal fluid from patients with progressive multifocal leukoencephalopathy

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242321
Author(s):  
Yi Luo ◽  
Nora Möhn ◽  
Amani Al-Mekhlafi ◽  
Sven Schuchardt ◽  
Thomas Skripuletz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Demyelinating Disease ◽  
Statistical Significance ◽  
Virus Detection ◽  
Normal Pressure ◽  
Csf Biomarkers ◽  
Diagnostic Biomarkers ◽  
Metabolomic Profiling ◽  
The Central Nervous System

Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential. However, diagnosis can be challenging if virus detection via cerebrospinal fluid (CSF) PCR remains negative. Hence, identifying CSF biomarkers for this disease is of crucial importance. We applied a targeted metabolomic screen to CSF from 23 PML patients and eight normal pressure hydrocephalus (NPH) patients as controls. Out of 188 potentially detectable metabolites, 48 (13 amino acids, 4 biogenic amines, 1 acylcarnitine, 21 phosphatidylcholines, 8 sphingolipids, and the sum of hexoses) passed the quality screen and were included in the analyses. Even though there was a tendency towards lower concentrations in PML (mostly of phosphatidylcholines and sphingomyelins), none of the differences between PML and controls in individual metabolite concentrations reached statistical significance (lowest p = 0.104) and there were no potential diagnostic biomarkers (highest area under the ROC curve 0.68). Thus, CSF metabolite changes in PML are likely subtle and possibly larger group sizes and broader metabolite screens are needed to identify potential CSF metabolite biomarkers for PML.

scholarly journals Circulating microRNAs as Potential Novel Diagnostic Biomarkers to Predict Drug Resistance in Temporal Lobe Epilepsy: A Pilot Study

2021 ◽  
Vol 22 (2) ◽  
pp. 702
Author(s):  
Selene De Benedittis ◽  
Francesco Fortunato ◽  
Claudia Cava ◽  
Francesca Gallivanone ◽  
Enrico Iaccino ◽  
...  
Keyword(s):  
Pilot Study ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Predictive Biomarkers ◽  
T Test ◽  
Drug Resistant ◽  
Diagnostic Biomarkers ◽  
Circulating Micrornas ◽  
Small Noncoding Rnas ◽  
Epigenetic Biomarkers

MicroRNAs (miRNAs) are small noncoding RNAs that have emerged as new potential epigenetic biomarkers. Here, we evaluate the efficacy of six circulating miRNA previously described in the literature as biomarkers for the diagnosis of temporal lobe epilepsy (TLE) and/or as predictive biomarkers to antiepileptic drug response. We measured the differences in serum miRNA levels by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays in a cohort of 27 patients (14 women and 13 men; mean ± SD age: 43.65 ± 17.07) with TLE compared to 20 healthy controls (HC) matched for sex, age and ethnicity (11 women and 9 men; mean ± SD age: 47.5 ± 9.1). Additionally, patients were classified according to whether they had drug-responsive (n = 17) or drug-resistant (n = 10) TLE. We have investigated any correlations between miRNAs and several electroclinical parameters. Three miRNAs (miR-142, miR-146a, miR-223) were significantly upregulated in patients (expressed as average expression ± SD). In detail, miR-142 expression was 0.40 ± 0.29 vs. 0.16 ± 0.10 in TLE patients compared to HC (t-test, p < 0.01), miR-146a expression was 0.15 ± 0.11 vs. 0.07 ± 0.04 (t-test, p < 0.05), and miR-223 expression was 6.21 ± 3.65 vs. 1.23 ± 0.84 (t-test, p < 0.001). Moreover, results obtained from a logistic regression model showed the good performance of miR-142 and miR-223 in distinguishing drug-sensitive vs. drug-resistant TLE. The results of this pilot study give evidence that miRNAs are suitable targets in TLE and offer the rationale for further confirmation studies in larger epilepsy cohorts.

scholarly journals Circulating miRNAs as Diagnostic and Prognostic Biomarkers in Common Solid Tumors: Focus on Lung, Breast, Prostate Cancers, and Osteosarcoma

2019 ◽  
Vol 8 (10) ◽  
pp. 1661 ◽  
Author(s):  
Michela Bottani ◽  
Giuseppe Banfi ◽  
Giovanni Lombardi
Keyword(s):  
Minimal Invasive ◽  
Circulating Mirnas ◽  
Validation Process ◽  
Diagnostic Biomarkers ◽  
Circulating Micrornas ◽  
Early Cancer Diagnosis ◽  
Specificity And Sensitivity ◽  
Cancer Types ◽  
Non Coding Rnas ◽  
Prostate Cancers

An early cancer diagnosis is essential to treat and manage patients, but it is difficult to achieve this goal due to the still too low specificity and sensitivity of classical methods (imaging, actual biomarkers), together with the high invasiveness of tissue biopsies. The discovery of novel, reliable, and easily collectable cancer markers is a topic of interest, with human biofluids, especially blood, as important sources of minimal invasive biomarkers such as circulating microRNAs (miRNAs), the most promising. MiRNAs are small non-coding RNAs and known epigenetic modulators of gene expression, with specific roles in cancer development/progression, which are next to be implemented in the clinical routine as biomarkers for early diagnosis and the efficient monitoring of tumor progression and treatment response. Unfortunately, several issues regarding their validation process are still to be resolved. In this review, updated findings specifically focused on the clinical relevance of circulating miRNAs as prognostic and diagnostic biomarkers for the most prevalent cancer types (breast, lung, and prostate cancers in adults, and osteosarcoma in children) are described. In addition, deep analysis of pre-analytical, analytical, and post-analytical issues still affecting the circulation of miRNAs’ validation process and routine implementation is included.

scholarly journals The Glymphatic Pathway: Waste Removal from the CNS via Cerebrospinal Fluid Transport

2017 ◽  
Vol 23 (5) ◽  
pp. 454-465 ◽  
Author(s):  
Helene Benveniste ◽  
Hedok Lee ◽  
Nora D. Volkow
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Fluid Transport ◽  
Key Factors ◽  
Waste Products ◽  
Anatomy And Physiology ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Glymphatic Pathway

The overall premise of this review is that cerebrospinal fluid (CSF) is transported within a dedicated peri-vascular network facilitating metabolic waste clearance from the central nervous system while we sleep. The anatomical profile of the network is complex and has been defined as a peri-arterial CSF influx pathway and peri-venous clearance routes, which are functionally coupled by interstitial bulk flow supported by astrocytic aquaporin 4 water channels. The role of the newly discovered system in the brain is equivalent to the lymphatic system present in other body organs and has been termed the “glymphatic pathway” or “(g)lymphatics” because of its dependence on glial cells. We will discuss and review the general anatomy and physiology of CSF from the perspective of the glymphatic pathway, a discovery which has greatly improved our understanding of key factors that control removal of metabolic waste products from the central nervous system in health and disease and identifies an additional purpose for sleep. A brief historical and factual description of CSF production and transport will precede the ensuing discussion of the glymphatic system along with a discussion of its clinical implications.

scholarly journals Long Non-Coding RNAs in Gliomas: From Molecular Pathology to Diagnostic Biomarkers and Therapeutic Targets

2018 ◽  
Vol 19 (9) ◽  
pp. 2754 ◽  
Author(s):  
Marek Vecera ◽  
Jiri Sana ◽  
Radim Lipina ◽  
Martin Smrcka ◽  
Ondrej Slaby
Keyword(s):  
Molecular Pathology ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Options ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Biological Behavior ◽  
Diagnostic Biomarkers ◽  
Non Coding Rnas

Gliomas are the most common malignancies of the central nervous system. Because of tumor localization and the biological behavior of tumor cells, gliomas are characterized by very poor prognosis. Despite significant efforts that have gone into glioma research in recent years, the therapeutic efficacy of available treatment options is still limited, and only a few clinically usable diagnostic biomarkers are available. More and more studies suggest non-coding RNAs to be promising diagnostic biomarkers and therapeutic targets in many cancers, including gliomas. One of the largest groups of these molecules is long non-coding RNAs (lncRNAs). LncRNAs show promising potential because of their unique tissue expression patterns and regulatory functions in cancer cells. Understanding the role of lncRNAs in gliomas may lead to discovery of the novel molecular mechanisms behind glioma biological features. It may also enable development of new solutions to overcome the greatest obstacles in therapy of glioma patients. In this review, we summarize the current knowledge about lncRNAs and their involvement in the molecular pathology of gliomas. A conclusion follows that these RNAs show great potential to serve as powerful diagnostic, prognostic, and predictive biomarkers as well as therapeutic targets.

Exosomes and Exosomal MicroRNAs in Age-Associated Stroke

2021 ◽  
Vol 19 ◽  
Author(s):  
Xiang Wang ◽  
Changmei HuangFu ◽  
Xiudeng Zhu ◽  
Jiehong Liu ◽  
Xinqin Gong ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Current Knowledge ◽  
Critical Role ◽  
Membrane Vesicles ◽  
Bioactive Molecules ◽  
Circulating Micrornas ◽  
Cell Functions ◽  
The Central Nervous System ◽  
Non Coding Rnas

Abstract: Aging has been considered to be the most important non-modifiable risk factor for stroke and death. Changes in circulation factors in the systemic environment, cellular senescence and artery hypertension during human ageing have been investigated. Exosomes are nanosize membrane vesicles that can regulate target cell functions via delivering their carried bioactive molecules (e.g. protein, mRNA, and microRNAs). In the central nervous system, exosomes and exosomal microRNAs play a critical role in regulating neurovascular function, and are implicated in the initiation and progression of stroke. MicroRNAs are small non-coding RNAs that have been reported to play critical roles in various biological processes. Recently, evidence has shown that microRNAs are packaged into exosomes and can be secreted into the systemic and tissue environment. Circulating microRNAs participate in cellular senescence and contribute to age-associated stroke. Here, we provide an overview of current knowledge on exosomes and their carried microRNAs in the regulation of cellular and organismal ageing processes, demonstrating the potential role of exosomes and their carried microRNAs in age-associated stroke.

scholarly journals Circulating MicroRNAs and Long Non-coding RNAs as Potential Diagnostic Biomarkers for Parkinson’s Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Yimin Yang ◽  
Yanhua Li ◽  
Hongmei Yang ◽  
Jianxing Guo ◽  
Nan Li
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Diagnostic Methods ◽  
Circulating Biomarkers ◽  
Diagnostic Biomarkers ◽  
Circulating Micrornas ◽  
Non Coding Rnas

Parkinson’s disease (PD) is the world’s second most common neurodegenerative disease that is associated with age. With the aging of the population, patients with PD are increasing in number year by year. Most such patients lose their ability to self-care with disease progression, which brings an incalculable burden to individual families and society. The pathogenesis of PD is complex, and its clinical manifestations are diverse. Therefore, it is of great significance to screen for circulating biomarkers associated with PD to reveal its pathogenesis and develop objective diagnostic methods so as to prevent, control, and treat the disease. In recent years, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are considered to be effective biomarkers for various diseases due to their stability, and resistance to RNAase digestion and extreme conditions in circulating fluids. Here, we review recent advances in the detection of abnormally expressed miRNAs and lncRNAs in PD circulating fluids, and discuss the function and molecular mechanisms of plasma or serum miR-124, miR-132, miR-29, miR-221, miR-7, miR-433, and miR-153 in the regulation and progression of PD. Additionally, application of the differential expression of lncRNAs in circulating fluid in the pathological progression and diagnosis of PD is also reviewed. In short, the determination of abnormally expressed circulating miRNAs and lncRNAs will be valuable for the future diagnosis and treatment of PD.

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