Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients

Ravanidis, Stylianos; Bougea, Anastasia; Papagiannakis, Nikolaos; Koros, Christos; Simitsi, Athina Maria; Pachi, Ioanna; Breza, Marianthi; Stefanis, Leonidas; Doxakis, Epaminondas

doi:10.1002/acn3.51146

Cited by 38 publications

(33 citation statements)

References 73 publications

(85 reference statements)

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“…These findings reinforce current knowledge that the etiology of PD is complex involving a mix of genetic and environmental influences on ageing brain. Similar findings have been observed in miRNA studies 62 . Further, a pool of four circRNAs discriminated subject with PD from controls with an AUC of 0.84.…”

Section: Discussionsupporting

confidence: 91%

Differentially expressed circular RNAs in peripheral blood mononuclear cells of PD patients

Ravanidis

Bougea

Karampatsi

et al. 2020

Preprint

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BackgroundNew noninvasive and affordable molecular approaches that will complement current practices and increase the accuracy of PD diagnosis are urgently needed. CircRNAs are highly stable non-coding RNAs that accumulate with aging in neurons and are increasingly shown to regulate all aspects of neuronal development and function.ObjectivesThe aims of the present study were to identify differentially expressed circRNAs in PBMCs of idiopathic PD patients and explore the competing endogenous RNA networks affected.MethodsEighty-seven circRNAs were initially selected based on relatively high gene expression in the human brain. Over half of these were readily detectable in PBMCs using RT-qPCR. Comparative expression analysis was then performed in PBMCs from sixty controls and sixty idiopathic subjects with PD.ResultsSix circRNAs derived from MAPK9, HOMER1, SLAIN1, DOP1B, REPS1, and PSEN1 transcripts were significantly downregulated in PD patients. The classifier that best distinguished PD consisted of four circRNAs with an AUC of 0.84. CLIP-Seq data revealed that the RNA binding proteins bound by most of the deregulated circRNAs include the neurodegeneration-associated FUS, TDP43, FMR1 and ATXN2. MicroRNAs predicted to be sequestered by most deregulated circRNAs had the GOslim categories ‘Protein modification’, ‘Transcription factor activity’ and ‘Cytoskeletal protein binding’ mostly enriched.ConclusionsThis is the first study that identifies circRNAs deregulated in the peripheral blood of PD patients. They may serve as diagnostic biomarkers and since they are highly expressed in the brain and are derived from genes with essential brain functions, they may also hint on the PD pathways affected.

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Section: Discussionsupporting

confidence: 91%

Differentially expressed circular RNAs in peripheral blood mononuclear cells of PD patients

Ravanidis

Bougea

Karampatsi

et al. 2020

Preprint

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“…These findings reinforce current knowledge that the etiology of PD is complex, involving a mix of genetic and environmental influences on aging brain. Similar findings have been observed in miRNA studies 62 . Further, a pool of four circRNAs discriminated patients with PD from control subjects with an AUC of 0.84.…”

Section: Discussionsupporting

confidence: 86%

Differentially Expressed Circular RNAs in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease

et al. 2021

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Background New noninvasive and affordable molecular approaches that will complement current practices and increase the accuracy of Parkinson's disease (PD) diagnosis are urgently needed. Circular RNAs (circRNAs) are stable noncoding RNAs that accumulate with aging in neurons and are increasingly shown to regulate all aspects of neuronal development and function. Objectives Τhe aims of this study were to identify differentially expressed circRNAs in blood mononuclear cells of patients with idiopathic PD and explore the competing endogenous RNA networks affected. Methods Eighty‐seven circRNAs were initially selected based on relatively high gene expression in the human brain. More than half of these were readily detectable in blood mononuclear cells using real‐time reverse transcription‐polymerase chain reaction. Comparative expression analysis was then performed in blood mononuclear cells from 60 control subjects and 60 idiopathic subjects with PD. Results Six circRNAs were significantly down‐regulated in patients with PD. The classifier that best distinguished PD consisted of four circRNAs with an area under the curve of 0.84. Cross‐linking immunoprecipitation‐sequencing data revealed that the RNA‐binding proteins bound by most of the deregulated circRNAs include the neurodegeneration‐associated FUS, TDP43, FMR1, and ATXN2. MicroRNAs predicted to be sequestered by most deregulated circRNAs have the Gene Ontology categories “protein modification” and “transcription factor activity” mostly enriched. Conclusions This is the first study that identifies specific circRNAs that may serve as diagnostic biomarkers for PD. Because they are highly expressed in the brain and are derived from genes with essential brain functions, they may also hint on the PD pathways affected. © 2021 Biomedical Research Foundation, Academy of Athens. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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“…miR-136-3p expression is also detected outside the CNS [ 64 , 65 , 66 ]. Circulating and CSF miR-136-3p levels are candidate biomarkers for both Parkinson’s disease and Alzheimer’s disease [ 67 , 68 , 69 , 70 ]. In patients with amyotrophic lateral sclerosis, serum miR-136-3p levels correlate with rapid disease progression [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury

Gupta

Ciszek

Heiskanen

et al. 2021

IJMS

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Noninvasive, affordable circulating biomarkers for difficult-to-diagnose mild traumatic brain injury (mTBI) are an unmet medical need. Although blood microRNA (miRNA) levels are reportedly altered after traumatic brain injury (TBI), their diagnostic potential for mTBI remains inconclusive. We hypothesized that acutely altered plasma miRNAs could serve as diagnostic biomarkers both in the lateral fluid percussion injury (FPI) model and clinical mTBI. We performed plasma small RNA-sequencing from adult male Sprague–Dawley rats (n = 31) at 2 days post-TBI, followed by polymerase chain reaction (PCR)-based validation of selected candidates. miR-9a-3p, miR-136-3p, and miR-434-3p were identified as the most promising candidates at 2 days after lateral FPI. Digital droplet PCR (ddPCR) revealed 4.2-, 2.8-, and 4.6-fold elevations in miR-9a-3p, miR-136-3p, and miR-434-3p levels (p < 0.01 for all), respectively, distinguishing rats with mTBI from naïve rats with 100% sensitivity and specificity. DdPCR further identified a subpopulation of mTBI patients with plasma miR-9-3p (n = 7/15) and miR-136-3p (n = 5/15) levels higher than one standard deviation above the control mean at <2 days postinjury. In sTBI patients, plasma miR-9-3p levels were 6.5- and 9.2-fold in comparison to the mTBI and control groups, respectively. Thus, plasma miR-9-3p and miR-136-3p were identified as promising biomarker candidates for mTBI requiring further evaluation in a larger patient population.

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Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients

Cited by 38 publications

References 73 publications

Differentially expressed circular RNAs in peripheral blood mononuclear cells of PD patients

Differentially expressed circular RNAs in peripheral blood mononuclear cells of PD patients

Differentially Expressed Circular RNAs in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease

Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury

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