Characterizing relevant microRNA editing sites in Parkinson’s disease

AbstractMicroRNAs (miRNAs) are extensively edited in human brains. However, the functional relevance of miRNA editome is largely unknown in Parkinson’s disease (PD). By analyzed small RNA sequencing profiles of brain tissues of 43 PD patients and 88 normal controls, we totally identified 421 miRNA editing sites with significantly different editing levels in prefrontal cortices of PD patients (PD-PC). A-to-I edited miR-497-5p has significantly higher expression levels in PD-PC compared to normal controls and directly represses OPA1 and VAPB, which potentially contributes to the progressive neurodegeneration of PD patients. These results provide new insights into mechanistic understanding, novel diagnostic and therapeutic clues of PD.

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Comprehensive analysis of human small RNA sequencing data provides insights into expression profiles and miRNA editing

RNA Biology ◽

10.1080/15476286.2014.996465 ◽

2014 ◽

Vol 11 (11) ◽

pp. 1375-1385 ◽

Cited By ~ 51

Author(s):

Jing Gong ◽

Yuliang Wu ◽

Xiantong Zhang ◽

Yifang Liao ◽

Vusumuzi Leroy Sibanda ◽

...

Keyword(s):

Rna Sequencing ◽

Small Rna ◽

Expression Profiles ◽

Comprehensive Analysis ◽

Small Rna Sequencing ◽

Sequencing Data ◽

Mirna Editing

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Alterations of Plasma Galectin-3 and C3 Levels in Patients with Parkinson’s Disease

Brain Sciences ◽

10.3390/brainsci11111515 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1515

Author(s):

Hsiu-Chuan Wu ◽

Kuo-Hsuan Chang ◽

Mu-Chun Chiang ◽

Chiung-Mei Chen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Peripheral Blood ◽

Plasma Levels ◽

Dopaminergic Neurons ◽

Cathepsin D ◽

The Other ◽

Galectin 3 ◽

Progressive Neurodegeneration ◽

Normal Controls

Parkinson’s disease (PD) is characterized by progressive neurodegeneration of dopaminergic neurons in the ventral midbrain. The complement-phagosome pathway is involved in the pathogenesis of PD. Here we measured levels of complement-phagocytosis molecules, including galectin-3, C3, C4, and cathepsin D, in the plasma of 56 patients with PD, and 46 normal controls (NCs). Plasma levels of galectin-3 (9.93 ± 3.94 ng/mL) were significantly higher in PD patients compared with NCs (8.39 ± 1.95 ng/mL, p = 0.012), and demonstrated a positive correlation with Hoehn and Yahr stages in PD patients (R2 = 0.218, p < 0.001). On the other hand, plasma C3 levels were significantly lower in PD patients (305.27 ± 205.16 μg/mL) compared with NCs (444.34 ± 245.54 μg/mL, p = 0.002). However, the levels did not correlate with Hoehn and Yahr stages (R2 = 0.010, p = 0.469). Plasma levels of C4 and cathepsin D in PD patients were similar to those in NCs. Our results show possible altered complement-phagocytosis signals in the peripheral blood of PD patients, highlighting the potential of galectin-3 as a biomarker of PD.

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Faculty Opinions recommendation of Identification of nutrient-responsive Arabidopsis and rapeseed microRNAs by comprehensive real-time polymerase chain reaction profiling and small RNA sequencing.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1161246.621733 ◽

2009 ◽

Author(s):

Alain Gojon

Keyword(s):

Polymerase Chain Reaction ◽

Real Time ◽

Rna Sequencing ◽

Small Rna ◽

Small Rna Sequencing ◽

Chain Reaction ◽

Polymerase Chain

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Faculty Opinions recommendation of Conditional expression of Parkinson's disease-related mutant α-synuclein in the midbrain dopaminergic neurons causes progressive neurodegeneration and degradation of transcription factor nuclear receptor related 1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717953615.793459220 ◽

2012 ◽

Author(s):

Patrik Brundin ◽

Jennifer Steiner

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Transcription Factor ◽

Nuclear Receptor ◽

Dopaminergic Neurons ◽

Midbrain Dopaminergic Neurons ◽

Conditional Expression ◽

Progressive Neurodegeneration

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Single-Cell RNA Sequencing in Parkinson’s Disease

Biomedicines ◽

10.3390/biomedicines9040368 ◽

2021 ◽

Vol 9 (4) ◽

pp. 368

Author(s):

Shi-Xun Ma ◽

Su Bin Lim

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Single Cell ◽

Rna Sequencing ◽

Rna Degradation ◽

Postmortem Brain ◽

Cell Type ◽

New Findings ◽

Postmortem Brain Tissue ◽

Technical Challenges

Single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have enhanced the understanding of the molecular pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). Nonetheless, their application in PD has been limited due mainly to the technical challenges resulting from the scarcity of postmortem brain tissue and low quality associated with RNA degradation. Despite such challenges, recent advances in animals and human in vitro models that recapitulate features of PD along with sequencing assays have fueled studies aiming to obtain an unbiased and global view of cellular composition and phenotype of PD at the single-cell resolution. Here, we reviewed recent sc/snRNA-seq efforts that have successfully characterized diverse cell-type populations and identified cell type-specific disease associations in PD. We also examined how these studies have employed computational and analytical tools to analyze and interpret the rich information derived from sc/snRNA-seq. Finally, we highlighted important limitations and emerging technologies for addressing key technical challenges currently limiting the integration of new findings into clinical practice.

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Small RNA Sequencing to Discover Circulating MicroRNA Biomarkers of Testicular Toxicity in Dogs

International Journal of Toxicology ◽

10.1177/1091581820961515 ◽

2020 ◽

pp. 109158182096151

Author(s):

Jennifer C. Shing ◽

Kai Schaefer ◽

Shaun E. Grosskurth ◽

Andy H. Vo ◽

Tatiana Sharapova ◽

...

Keyword(s):

Rna Sequencing ◽

Small Rna ◽

Exploratory Study ◽

Quantitative Polymerase Chain Reaction ◽

Small Rna Sequencing ◽

Circulating Microrna ◽

Testicular Toxicity ◽

Potential Candidate ◽

Drug Induced ◽

Organ Systems

Predictive indicators of testicular toxicity could improve drug development by allowing early in-life screening for this adverse effect before it becomes severe. We hypothesized that circulating microRNAs (miRNAs) could serve as testicular toxicity biomarkers in dogs. Herein, we describe the results of an exploratory study conducted to discover biomarkers of drug-induced testicular injury. Following a dose-selection study using the testicular toxicant ethylene glycol monomethyl ether (EGME), we chose a dose of 50 mg/kg/d EGME to avoid systemic toxicity and treated 2 groups of dogs (castrated, non-castrated) for 14 to 28 days. Castrated animals were used as negative controls to identify biomarkers specific for testicular toxicity because EGME can cause toxicity to organ systems in addition to the testis. Blood was collected daily during the dosing period, followed by recovery for 29 to 43 days with less frequent sampling. Dosing was well tolerated, resulting in mild-to-moderate degeneration in testes and epididymides. Global profiling of serum miRNAs at selected dosing and recovery time points was completed by small RNA sequencing. Bioinformatics data analysis using linear modeling demonstrated several circulating miRNAs that were differentially abundant during the dosing period compared with baseline and/or castrated control samples. Confirmatory reverse transcription quantitative polymerase chain reaction data in these animals was unable to detect sustained alterations of miRNAs in serum, except for 1 potential candidate cfa-miR-146b. Taken together, we report the results of a comprehensive exploratory study and suggest future directions for follow-up research to address the challenge of developing diagnostic biomarkers of testicular toxicity.

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Small RNA-Sequencing: Approaches and Considerations for miRNA Analysis

Diagnostics ◽

10.3390/diagnostics11060964 ◽

2021 ◽

Vol 11 (6) ◽

pp. 964

Author(s):

Sarka Benesova ◽

Mikael Kubista ◽

Lukas Valihrach

Keyword(s):

Rna Sequencing ◽

Small Rna ◽

High Sensitivity ◽

Small Rna Sequencing ◽

Rna Seq ◽

Liquid Biopsies ◽

Comprehensive Overview ◽

Rna Molecules ◽

Novel Mirna ◽

The Many

MicroRNAs (miRNAs) are a class of small RNA molecules that have an important regulatory role in multiple physiological and pathological processes. Their disease-specific profiles and presence in biofluids are properties that enable miRNAs to be employed as non-invasive biomarkers. In the past decades, several methods have been developed for miRNA analysis, including small RNA sequencing (RNA-seq). Small RNA-seq enables genome-wide profiling and analysis of known, as well as novel, miRNA variants. Moreover, its high sensitivity allows for profiling of low input samples such as liquid biopsies, which have now found applications in diagnostics and prognostics. Still, due to technical bias and the limited ability to capture the true miRNA representation, its potential remains unfulfilled. The introduction of many new small RNA-seq approaches that tried to minimize this bias, has led to the existence of the many small RNA-seq protocols seen today. Here, we review all current approaches to cDNA library construction used during the small RNA-seq workflow, with particular focus on their implementation in commercially available protocols. We provide an overview of each protocol and discuss their applicability. We also review recent benchmarking studies comparing each protocol’s performance and summarize the major conclusions that can be gathered from their usage. The result documents variable performance of the protocols and highlights their different applications in miRNA research. Taken together, our review provides a comprehensive overview of all the current small RNA-seq approaches, summarizes their strengths and weaknesses, and provides guidelines for their applications in miRNA research.

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