A panel of four decreased serum microRNAs as a novel biomarker for early Parkinson’s disease

Dong, Hui; Wang, Cheng; Lu, Sunbin; Yu, Cuiyu; Huang, Lei; Feng, Weixi; Xu, Hui; Chen, Xi; Zen, Ke; Qiao, Yan; Liu, Weiguo; Zhang, Chenyu

doi:10.3109/1354750x.2015.1118544

Cited by 100 publications

(86 citation statements)

References 41 publications

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“…Other miRNAs reported by several PD studies, such as miR-133b, -34c-5p, -205,-155, -135b, -212, -495, -193a-3p, -34b/c and -485-5p, shared the similar expression regulation with our result, but their fold-change was lower and didn't meet our inclusion criteria [59, 61–63, 68–70]. However, the miR-214, -124, -132, -127-5p, -146b-5p, and -16-5p reported in other PD models, were not found the different expression [26, 30, 54, 55, 57, 60]. And some PD-related miRNAs, included miR-7, -153, -1224, -184 and let-7i-3p, were just changed slightly in our results [23, 51–53].…”

Section: Discussionsupporting

confidence: 78%

“…Several miRNAs were found with different expression levels in PD models, such as miR-135a-5p, -214 and -124 in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mice [55–58], miR-155 in AAV-α-Syn PD mice [59], and miR-10a, -10b, -212, -132, -495 in A30P tg mice [26]. In PD patients, the deficient expressions was demonstrated on miR-141, -214, -146b-5p, -193a-3p, -133b, -433, -34b/c and -205 [24, 60–63], and other different signatures of 29 miRNAs in brain [64]. Here we used deep sequencing technique for miRNAs analysis, this technical method is independent of the miRNA database and provides better accuracy and precision on miRNAs detection [65].…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian

Xiao

Huang

et al. 2016

Oncotarget

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α-synuclein gene mutations can cause α-synuclein protein aggregation in the midbrain of Parkinson's disease (PD) patients. MicroRNAs (miRNAs) play a key role in the metabolism of α-synuclein but the mechanism involved in synucleinopathy remains unclear. In this study, we investigated the miRNA profiles in A53T-α-synuclein transgenic mice and analyzed the candidate miRNAs in the cerebrospinal fluid (CSF) of PD patients. The 12-month A53T-transgenic mouse displayed hyperactive movement and anxiolytic-like behaviors with α-synuclein aggregation in midbrain. A total of 317,759 total and 289,207 unique small RNA sequences in the midbrain of mice were identified by high-throughput deep sequencing. We found 644 miRNAs were significantly changed in the transgenic mice. Based on the conserved characteristic of miRNAs, we selected 11 candidates from the 40 remarkably expressed miRNAs and explored their expression in 44 CSF samples collected from PD patients. The results revealed that 11 microRNAs were differently expressed in CSF, emphatically as miR-144-5p, miR-200a-3p and miR-542-3p, which were dramatically up-regulated in both A53T-transgenic mice and PD patients, and had a helpful accuracy for the PD prediction. The ordered logistic regression analysis showed that the severity of PD has strong correlation with an up-expression of miR-144-5p, miR-200a-3p and miR-542-3p in CSF. Taken together, our data suggested that miRNAs in CSF, such as miR-144-5p, miR-200a-3p and miR-542-3p, may be useful to the PD diagnosis as potential biomarkers.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian

Xiao

Huang

et al. 2016

Oncotarget

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“…Exogenous synthesized miRNAs such as Caenorhabditis elegans miR-39/54/238 are also used for normalization (Mitchell et al, 2008; Brase et al, 2011; Tan et al, 2014), which, however, lack the capacity to normalize biological and pathological variations (Laurent et al, 2015). In general, higher amount of qPCR template can reduce the cycle number and obtain lower Ct value for potentially more stable values, and larger sample size helps the power of analysis (Dong et al, 2016). Unfortunately, there is realistic challenges to acquire more volume and more samples such as in the study by Muller et al (2014).…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned earlier, we selected the six miRNAs based on postmortem evidence in brain and/or regulating α-synuclein expression. Not considering the studies which measure miRNAs individually selected by their respective rationales, results from screenings by arrays or next generation sequencing are surprisingly rarely overlapped (Martins et al, 2011; Khoo et al, 2012; Cardo et al, 2013; Soreq et al, 2013; Botta-Orfila et al, 2014; Burgos et al, 2014; Vallelunga et al, 2014; Gui et al, 2015; Ding et al, 2016; Dong et al, 2016). 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.…”

Section: Discussionmentioning

confidence: 99%

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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“…All the miRNAs are involved in the inflammation/immunity system on PD pathogenesis [54]. Furthermore, the decreased level of miR-141, miR-214、miR-146b-5p and miR-193a-3p was found closely associated with the early stage of PD [55]. In our study, there were 644 abnormal miRNAs detected in A53T-PD transgenic mice using high-throughput screening.…”

Section: Microrna Signatures In Pdmentioning

confidence: 68%

The biomarkers of immune dysregulation and inflammation response in Parkinson disease

Chen

et al. 2016

Transl Neurodegener

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Parkinson’s disease (PD) is referring to the multi-systemic α-synucleinopathy with Lewy bodies deposited in midbrain. In ageing, the environmental and genetic factors work together and overactive major histocompatibility complex pathway to regulate immune reactions in central nerve system which resulting in neural degeneration, especially in dopaminergic neurons. As a series of biomarkers, the human leukocyte antigen genes with its related proteomics play cortical roles on the antigen presentation of major histocompatibility complex molecules to stimulate the differentiation of T lymphocytes and i-proteasome activities under their immune response to the PD-related environmental alteration and genetic variation. Furthermore, dopaminergic drugs change the biological characteristic of T lymphatic cells, affect the α-synuclein presentation pathway, and inhibit T lymphatic cells to release cytotoxicity in PD development. Taking together, the serum inflammatory factors and blood T cells are involved in the immune dysregulation of PD and inspected as the potential clinic biomarkers for PD prediction.

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A panel of four decreased serum microRNAs as a novel biomarker for early Parkinson’s disease

Abstract: The four serum miRNAs may represent novel biomarkers for the early detection of PD.

Cited by 100 publications

References 41 publications

MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian

MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian

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

The biomarkers of immune dysregulation and inflammation response in Parkinson disease

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