MicroRNA isolation and quantification in cerebrospinal fluid: A comparative methodical study

Kopková, Alena; Šána, Jiří; Fadrus, Pavel; Macháčková, Táňa; Večeřa, Marek; Vybíhal, Václav; Juráček, Jaroslav; Vychytilova-Faltejskova, Petra; Smrčka, Martin; Slabý, Ondřej

doi:10.1371/journal.pone.0208580

Cited by 19 publications

(25 citation statements)

References 25 publications

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“…However, analysis of these small non-coding RNAs in CSF is still not fully standardized and there are many factors that could bias the results. Thus, optimization and standardization of individual steps of the whole analytical process could bring CSF miRNAs closer to the clinical utilization [26].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors

Kopková

Šána

Macháčková

et al. 2019

Cancers

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Central nervous system (CNS) malignancies include primary tumors that originate within the CNS as well as secondary tumors that develop as a result of metastatic spread. Circulating microRNAs (miRNAs) were found in almost all human body fluids including cerebrospinal fluid (CSF), and they seem to be highly stable and resistant to even extreme conditions. The overall aim of our study was to identify specific CSF miRNA patterns that could differentiate among brain tumors. These new biomarkers could potentially aid borderline or uncertain imaging results onto diagnosis of CNS malignancies, avoiding most invasive procedures such as stereotactic biopsy or biopsy. In total, 175 brain tumor patients (glioblastomas, low-grade gliomas, meningiomas and brain metastases), and 40 non-tumor patients with hydrocephalus as controls were included in this prospective monocentric study. Firstly, we performed high-throughput miRNA profiling (Illumina small RNA sequencing) on a discovery cohort of 70 patients and 19 controls and identified specific miRNA signatures of all brain tumor types tested. Secondly, validation of 9 candidate miRNAs was carried out on an independent cohort of 105 brain tumor patients and 21 controls using qRT-PCR. Based on the successful results of validation and various combination patterns of only 5 miRNA levels (miR-30e, miR-140, let-7b, mR-10a and miR-21-3p) we proposed CSF-diagnostic scores for each tumor type which enabled to distinguish them from healthy donors and other tumor types tested. In addition to this primary diagnostic tool, we described the prognostic potential of the combination of miR-10b and miR-196b levels in CSF of glioblastoma patients. In conclusion, we performed the largest study so far focused on CSF miRNA profiling in patients with brain tumors, and we believe that this new class of biomarkers have a strong potential as a diagnostic and prognostic tool in these patients.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors

Kopková

Šána

Macháčková

et al. 2019

Cancers

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“…miR-1 is a highly conserved miRNA that is detected in muscle, neurons and circulatory body fluid of multiple metazoan phyla (de Rie et al, 2017; Kopkova et al, 2018; Kusuda et al, 2011; Sokol, 2012) (Figure 1A). Multiple roles of miR-1 have been identified in the development and function of muscle in multiple systems (Simon et al, 2008; Sokol and Ambros, 2005; Zhao et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

Nehammer¹,

Ejlerskov

Gopal

et al. 2019

eLife

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Appropriate regulation of autophagy is crucial for clearing toxic proteins from cells. Defective autophagy results in accumulation of toxic protein aggregates that detrimentally affect cellular function and organismal survival. Here, we report that the microRNA miR-1 regulates the autophagy pathway through conserved targeting of the orthologous Tre-2/Bub2/CDC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in Caenorhabditis elegans and mammalian cells, respectively. Loss of miR-1 causes TBC-7/TBC1D15 overexpression, leading to a block on autophagy. Further, we found that the cytokine interferon-β (IFN-β) can induce miR-1 expression in mammalian cells, reducing TBC1D15 levels, and safeguarding against proteotoxic challenges. Therefore, this work provides a potential therapeutic strategy for protein aggregation disorders.

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“…In addition, free circulating miRNA in blood stream can be originated from platelets and blood cells (Wang, Yuan, et al, 2012) and constitute important contaminants in exosomal preparations. The lack of standardized protocols to miRNA analysis is an important limitation, particularly in the case of CSF that render in lower RNA yields than blood (Kopkova et al., 2018).…”

Section: Exosomes As Biomarker Resources In Admentioning

confidence: 99%

Diagnostic and therapeutic potential of exosomes in Alzheimer’s disease

Martins

Trindade

Vaz

et al. 2020

Journal of Neurochemistry

121

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Exosomes are small extracellular vesicles released by almost all cell types in physiological and pathological conditions. The exosomal potential to unravel disease mechanisms, or to be used as a source of biomarkers, is being explored, in particularly in the field of neurodegenerative diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world and exosomes appear to have a relevant role in disease pathogenesis. This review summarizes the current knowledge on exosome contributions to AD as well as their use as disease biomarker resources or therapeutic targets. The most recent findings with respect to both protein and miRNA biomarker candidates for AD, herein described, highlight the state of the art in this field and encourage the use of exosomes derived from biofluids in clinical practice in the near future.

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MicroRNA isolation and quantification in cerebrospinal fluid: A comparative methodical study

Cited by 19 publications

References 25 publications

Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors

Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors

Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

Diagnostic and therapeutic potential of exosomes in Alzheimer’s disease

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