MicroRNA biomarkers of Parkinson’s disease in serum exosome-like microvesicles

Cao, Xiangyang; Lu, Jing‐Min; Zhao, Zhiqiang; Li, Mingchao; Lu, Ting; An, Xizhong; Xue, Liujun

doi:10.1016/j.neulet.2017.02.045

Cited by 163 publications

(125 citation statements)

References 28 publications

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“…We also observed a systematic decline in miRNA expression over time, revealing a signature of miRNAs associated with leukocytes, in particular monocytes and B cells, as well as exosomes and RBCs. Among these are several members of the miR-19 and miR-29 families that are consistent with earlier findings [33][34][35][36][37] . Also, PD induced changes for both monocyte and exosome expression signatures has been reported in several other studies [38][39][40][41] .…”

Section: Discussionsupporting

confidence: 91%

Deep sncRNA-seq of the PPMI cohort to study Parkinson’s disease progression

Kern

Fehlmann

Violich

et al. 2020

Preprint

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Coding and non-coding RNAs have diagnostic and prognostic importance in Parkinson's diseases (PD). We studied circulating small non-coding RNAs (sncRNAs) in 7, 003 samples from two longitudinal PD cohorts (Parkinson's Progression Marker Initiative (PPMI) and Luxembourg Parkinson's Study (NCER-PD)) and modelled their influence on the transcriptome. First, we sequenced sncRNAs in 5, 450 blood samples of 1, 614 individuals in PPMI. The majority of 323 billion reads (59 million reads per sample) mapped to miRNAs. Other covered RNA classes include piRNAs, rRNAs, snoRNAs, tRNAs, scaRNAs, and snRNAs. De-regulated miRNAs were associated with the disease and disease progression and occur in two distinct waves in the third and seventh decade of live. Originating mostly from a characteristic set of immune cells they resemble a systemic inflammation response and mitochondrial dysfunction, two hallmarks of PD. By profiling 1, 553 samples from 1, 024 individuals in the NCER-PD cohort using an independent technology, we validate relevant findings from the sequencing study. Finally, network analysis of sncRNAs and transcriptome sequencing of the original cohort identified regulatory modules emerging in progressing PD patients.miRNA studies to date, covering over 3, 000 patients and controls 21 .Advanced biomarker studies however require carefully designed cohorts. Already a few large-scale PD studies aiming to advance diagnosis, prognosis and therapeutics fulfil respective requirements 22-24 . Among them, the Parkinson's Progression Marker Initiative (PPMI) is a multi-cohort, longitudinal observational study designed to discover and validate objective biomarkers of Parkinson's 25 . The PPMI project constitutes a global effort of 33 clinical sites in 11 countries with regular study participant assessments (Figure 1a). It also features comprehensive clinical phenotyping to observe hundreds of characteristics of the known subtypes of the disease, such as the idiopathic and genetic forms. Further, longitudinal biosampling following rigorous Standard Operating Procedures (SOPs) is performed to set a framework for the discovery and validation of early-onset and prognostic biomarkers. To identify potential non-coding RNA and transcriptomic markers in PPMI we performed RNA-seq on blood samples drawn at each clinical visit. For short and long RNAs, we carried out optimized assays and sequenced separate aliquots from the same blood samples for paired RNA analyses. Here, we present the evaluation of the sncRNA-seq fraction for disease detection and progression tracking. We examine the potential of different classes of small RNAs but emphasise the role of miRNAs. We also validate relevant findings for miRNAs on the Luxembourg Parkinson's Study in the framework of the National Centre for Excellence in Research on PD (NCER-PD) cohort 22 , which was performed independently and with a different technology. Finally, we provide insights on how the key non-coding RNAs regulate gene expression by utilizing the long RNA sequencing data. Specific ana...

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Section: Discussionsupporting

confidence: 91%

Deep sncRNA-seq of the PPMI cohort to study Parkinson’s disease progression

Kern

Fehlmann

Violich

et al. 2020

Preprint

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“…This discrepancy may be attributed to differences in ages, disease stages and subtypes of included patients, threshold of significance in data processing, sample sizes, and type of sources if using different fluids/cells. Of note from the overall results, a decreased level of miR-19b/miR-19b-3p in PD is suggested by four studies, respectively, in PBMCs (Martins et al, 2011), serum (Botta-Orfila et al, 2014; Cao et al, 2017), and CSF (Gui et al, 2015), except one study which shows increased miR-19b-3p expression in CSF (Burgos et al, 2014). The expression of miR-195 is suggested increased in serum of PD by two studies (Ding et al, 2016; Cao et al, 2017).…”

Section: Discussionmentioning

confidence: 77%

“…Of note from the overall results, a decreased level of miR-19b/miR-19b-3p in PD is suggested by four studies, respectively, in PBMCs (Martins et al, 2011), serum (Botta-Orfila et al, 2014; Cao et al, 2017), and CSF (Gui et al, 2015), except one study which shows increased miR-19b-3p expression in CSF (Burgos et al, 2014). The expression of miR-195 is suggested increased in serum of PD by two studies (Ding et al, 2016; Cao et al, 2017). The expression of miR-30c is decreased in PD, respectively, in PBMCs (Martins et al, 2011) and serum (Vallelunga et al, 2014).…”

Section: Discussionmentioning

confidence: 77%

Reduced Circulating Levels of miR-433 and miR-133b Are Potential Biomarkers for Parkinson’s Disease

Zhang

Yang

et al. 2017

Front. Cell. Neurosci.

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Aberrant expression of microRNA (miRNA) in tissues may lead to altered level in circulation. Considerable evidence has suggested that miRNA deregulation is involved in the pathogenesis of Parkinson’s disease (PD). In this study, we screened a set of PD-associated miRNAs and aimed to identify differentially expressed miRNAs in plasma of PD patients and to evaluate their potentiality to serve as PD biomarkers. A total of 95 subjects consisting of 46 sporadic PD cases and 49 controls were recruited. Plasma levels of six miRNAs including miR-433, miR-133b, miR-34b, miR-34c, miR-153, and miR-7 were evaluated using reverse transcribed quantitative PCR, among which we found that miR-34c and miR-7 were below detection limit under our condition. The results showed that levels of circulating miR-433 (P = 0.003) and miR-133b (P = 0.006), but not miR-34b and miR-153, were reduced in PD patients. miR-433 and miR-133b were strongly correlated in both control and PD groups (rs = 0.87 and 0.85, respectively). The correlation between miR-34b and miR-153 expressions was significantly reduced (P < 0.05) in the PD group. Although miR-433 and miR-133b were likely to be functionally complimentary as suggested by Pathway and Gene Ontology analyses, these two miRNAs per se might not be sufficient to predict PD. No correlation was observed between the four miRNAs and age or severity of disease. Collectively, our results demonstrate that circulating miR-433 and miR-133b are significantly altered in PD and may serve as PD biomarkers.

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“…In addition, ROC curve analysis revealed that these six ex-miRNAs are ideal biomarkers for the diagnosis of PD, but the researchers also mentioned that, because of the small number of patients enrolled, subsequent larger multicenter studies were needed to verify their conclusions. Another differential expression study of serum-derived ex-miRNA was performed by Cao et al (2017). Comparison of the levels of 24 ex-miRNAs from the serum of 109 PD patients and healthy controls showed that the levels of ex-miR-24 (AUC, 0.908; 95% CI, 0.850-0.949) and ex-miR-195 (AUC, 0.697; 95% CI, 0.617-0.770) were increased, and ex-miR-19b (AUC, 0.753; 95% CI, 0.675-0.820) decreased in PD patients, indicating the possible use of ex-miRNA as a novel strategy for the diagnosis of PD.…”

Section: Ex-mirnas As Biomarkers In Pdmentioning

confidence: 99%

Circulating Exosomal miRNA as Diagnostic Biomarkers of Neurodegenerative Diseases

Wang

Zhang

2020

Front. Mol. Neurosci.

100

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Neurodegenerative diseases (NDDs) are a group of diseases caused by chronic and progressive degeneration of neural tissue. The main pathological manifestations are neuronal degeneration and loss in the brain and/or spinal cord. Common NDDs include Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD), and amyotrophic lateral sclerosis (ALS). The complicated pathological characteristics and different clinical manifestations of NDDs result in a lack of sensitive and efficient diagnostic methods. In addition, no sensitive biomarkers are available to monitor the course of NDDs, predict their prognosis, and monitor the therapeutic response. Despite extensive research in recent years, analysis of amyloid β (Aβ) and α-synuclein has failed to effectively improve NDD diagnosis. Although recent studies have indicated circulating miRNAs as promising diagnostic biomarkers of NDDs, the miRNA in the peripheral circulation is susceptible to interference by other components, making circulating miRNA results less consistent. Exosomes are small membrane vesicles with a diameter of approximately 30-100 nm that transport proteins, lipids, mRNA, and miRNA. Because recent studies have shown that exosomes have a double-membrane structure that can resist ribonuclease in the blood, giving exosomal miRNA high stability and making them resistant to degradation, they may become an ideal biomarker of circulating fluids. In this review, we discuss the applicability of circulating exosomal miRNAs as biomarkers, highlight the technical aspects of exosomal miRNA analysis, and review studies that have used circulating exosomal miRNAs as candidate diagnostic biomarkers of NDDs.

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MicroRNA biomarkers of Parkinson’s disease in serum exosome-like microvesicles

Cited by 163 publications

References 28 publications

Deep sncRNA-seq of the PPMI cohort to study Parkinson’s disease progression

Deep sncRNA-seq of the PPMI cohort to study Parkinson’s disease progression

Reduced Circulating Levels of miR-433 and miR-133b Are Potential Biomarkers for Parkinson’s Disease

Circulating Exosomal miRNA as Diagnostic Biomarkers of Neurodegenerative Diseases

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