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

Zhang, Xiong; Yang, Rui; Hu, Bei‐Lei; Lu, Pengcheng; Zhou, Lili; He, Zelai; Wang, Hongmei; Zhu, Jian-Hong

doi:10.3389/fncel.2017.00170

Cited by 58 publications

(65 citation statements)

References 60 publications

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“…In the present study, the serum level of miR-133b was significantly downregulated in AD patients, which was consistent with the results of previous studies on PD patients (14,15). The expression of miR-133b was also assessed in the human neuroblastoma cell line SH-SY5Y.…”

Section: Discussionsupporting

confidence: 92%

“…AD and Parkinson's disease (PD) all belong to neurodegenerative diseases, which are characterized by neurodegenerative changes and brain dysfunction (13). Furthermore, multiple studies have proved the abnormal expression of miR-133b in PD patients, indicating the crucial role of miR-133b in this neurodegenerative disease (14)(15)(16). However, to date, the expression and role of miR-133b in the development of AD have remained to be fully determined.…”

Section: Introductionmentioning

confidence: 99%

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miR‑133b is a potential diagnostic biomarker for Alzheimer's disease and has a neuroprotective role

2019

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MicroRNAs (miRNAs/miRs) are involved in post-transcriptional gene regulation and aberrant expression of miRNAs has been widely detected in various human diseases. The aim of the present study was to examine the serum levels of miR-133b in patients with Alzheimer's disease (AD), and to explore its diagnostic value and neuroprotective role in AD. Reverse transcription-quantitative PCR was applied to analyze the serum levels of miR-133b in 105 AD patients and 98 healthy controls. A cell model of AD was established by treating SH-SY5Y cells with amyloid β (Aβ)25-35, and the resulting effect on miR-133b expression was determined. Cell viability and apoptosis were also measured. A dual-luciferase assay was used to validate a target gene of miR-133b. Receiver operating characteristic (ROC) curve analysis was also applied to assess the specificity and sensitivity of miR-133b to diagnose AD. The results indicated that the serum levels of miR-133b were significantly downregulated in AD patients and SH-SY5Y cells treated with Aβ25-35 (all P<0.001). A positive correlation between the serum levels of miR-133b and the Mini-Mental State Examination score of AD patients was determined (r=0.8814, P<0.001). The area under the ROC curve for miR-133b regarding the diagnosis of AD was 0.907, with a sensitivity of 90.8% and specificity of 74.3% at the cutoff value of 1.70. Overexpression of miR-133b significantly attenuated the Aβ25-35-induced inhibition of cell viability (P<0.01) and induction of cell apoptosis (P<0.01). The luciferase reporter assay demonstrated that epidermal growth factor receptor (EGFR) is a target gene of miR-133b. In conclusion, miR-133b may serve as a novel diagnostic biomarker for AD and it may have a neuroprotective role in AD and targets EGFR.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

miR‑133b is a potential diagnostic biomarker for Alzheimer's disease and has a neuroprotective role

2019

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“…Of the 8 miRNAs that were differentially expressed between iPD and controls, 4 (50%) have been previously identified as deregulated in PD. These were miR‐7‐5p, miR‐22‐3p, miR‐124‐3p, and miR‐433‐3p . Another interesting finding is that the miRNAs found deregulated in genetic versus iPD cases were very different.…”

Section: Discussionmentioning

confidence: 95%

“…These were miR-7-5p, 71 miR-22-3p, [72][73][74] miR-124-3p, 75 and miR-433-3p. 76 Another interesting finding is that the miRNAs found deregulated in genetic versus iPD cases were very different. miR-136-3p was the only common miRNA found deregulated in both idiopathic and genetic PD cohorts; however, although its expression was increased in iPD, levels were decreased in genetic cases.…”

Section: Discussionmentioning

confidence: 99%

Circulating Brain‐Enriched MicroRNAs for Detection and Discrimination of Idiopathic and Genetic Parkinson's Disease

et al. 2019

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Background A minimally invasive test for early detection and monitoring of Parkinson's disease (PD) is a highly unmet need for drug development and planning of patient care. Blood plasma represents an attractive source of biomarkers. MicroRNAs (miRNAs) are conserved noncoding RNA molecules that serve as posttranscriptional regulators of gene expression. As opposed to ubiquitously expressed miRNAs that control house‐keeping processes, brain‐enriched miRNAs regulate diverse aspects of neuron development and function. These include neuron‐subtype specification, axonal growth, dendritic morphogenesis, and spine density. Backed by a large number of studies, we now know that the differential expression of neuron‐enriched miRNAs leads to brain dysfunction. Objectives The aim was to identify subsets of brain‐enriched miRNAs with diagnostic potential for familial and idiopathic PD as well as specify the molecular pathways deregulated in PD. Methods Initially, brain‐enriched miRNAs were selected based on literature review and validation studies in human tissues. Subsequently, real‐time reverse transcription polymerase chain reaction was performed in the plasma of 100 healthy controls and 99 idiopathic and 53 genetic (26 alpha‐synucleinA53T and 27 glucocerebrosidase) patients. Statistical and bioinformatics analyses were carried out to pinpoint the diagnostic biomarkers and deregulated pathways, respectively. Results An explicit molecular fingerprint for each of the 3 PD cohorts was generated. Although the idiopathic PD fingerprint was different from that of genetic PD, the molecular pathways deregulated converged between all PD subtypes. Conclusions The study provides a group of brain‐enriched miRNAs that may be used for the detection and differentiation of PD subtypes. It has also identified the molecular pathways deregulated in PD. © 2019 International Parkinson and Movement Disorder Society

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“…Several groups, including our own, have linked miR-153 and, to a lesser extent, miR-223 to PD pathology. 30,31,33,39 Alterations in miR-153 levels have been documented in PD CSF 41 and plasma, 43 whereas changes in miR-223 have been reported in PD serum. 39 Differential expression of miR-153 and miR-223 has been reported in other central nervous system conditions.…”

Section: Discussionmentioning

confidence: 99%

Salivary microR‐153 and microR‐223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease

et al. 2019

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Background Parkinson's disease (PD) is the most common movement disorder among adults, affecting 2% of the world population older than 65 years of age. No diagnostic biomarker for routine use in clinical settings currently exists. Dysregulation of microRNAs (miRNAs) has been implicated in various neurodegenerative conditions, including PD. Distinct miRNAs have been demonstrated to be involved in the regulation of α‐synuclein, a key player in PD pathogenesis; miR‐153 and miR‐223 are downregulated in the brain and serum of parkinsonian GFAP.HMOX1 transgenic mice where they directly regulate α‐synuclein. Objective To ascertain whether salivary miR‐153 and miR‐223 are similarly downmodulated in, and may serve as diagnostic biomarkers of, idiopathic PD. Methods Using reverse transcriptase quantitative polymerase chain reaction, miR‐153 and miR‐223 levels were evaluated in the saliva of 77 non‐neurological controls and 83 PD patients. Levels of heme oxygenase‐1 and α‐synuclein were measured using enzyme‐linked immunosorbent assay. Analyses were adjusted by age, sex, medication exposure, disease duration, and relevant comorbidities. Results Log‐transformed expression levels of miR‐153 and miR‐223 were significantly decreased in the saliva of human PD patients in comparison with nonneurological controls. The miRNA expression levels did not change as a function of disease progression (Hoehn and Yahr staging). The area under the receiver operating characteristic curve separating controls from PD patients was 79% (95% confidence interval, 61%–96%) for miR‐153 and 77% (95% confidence interval, 59%–95%) for miR‐223. The ratios of miRNAs to oligomeric α‐synuclein, total α‐synuclein, or heme oxygenase‐1 protein did not improve accuracy of the test. Conclusion Salivary miR‐153 and miR‐223 levels may serve as useful, noninvasive, and relatively inexpensive diagnostic biomarkers of idiopathic PD. © 2019 International Parkinson and Movement Disorder Society

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

Cited by 58 publications

References 60 publications

miR‑133b is a potential diagnostic biomarker for Alzheimer's disease and has a neuroprotective role

miR‑133b is a potential diagnostic biomarker for Alzheimer's disease and has a neuroprotective role

Circulating Brain‐Enriched MicroRNAs for Detection and Discrimination of Idiopathic and Genetic Parkinson's Disease

Salivary microR‐153 and microR‐223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease

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