The emerging role of microRNA-4487/6845-3p in Alzheimer’s disease pathologies is induced by Aβ25–35 triggered in SH-SY5Y cell

Hu, Ling; Zhang, Rong; Yuan, Qiong; Gao, Yinping; Yang, Mary Qu; Zhang, Chunxiang; Huang, Jiankun; Sun, Yufei; Yang, William; Zhou, Min; Cheng, Jun; Deng, Youping; Hu, Xingjian

doi:10.1186/s12918-018-0633-3

Cited by 25 publications

(13 citation statements)

References 35 publications

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“…The combination of three miRNAs (miR-574-5p, miR-6165, miR-6760-5p), showed a good clinical performance (AUC = 0.9492) with a sensitivity of 87.5% and a specificity of 87.5% for predicting MMD. The dysregulated miRNAs have previously been implicated in cases of neuroinflammation and deteriorated synaptic function, subarachnoid hemorrhage, acute stroke and hematoma enlargement (Zheng et al, 2012;Hu et al, 2018). Of note, three of the four dysregulated miRNAs are up-regulated and thus suggest there is a repression of the targets in the enriched pathways.…”

Section: Discussionmentioning

confidence: 93%

A Panel of Exosome-Derived miRNAs of Cerebrospinal Fluid for the Diagnosis of Moyamoya Disease

et al. 2020

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Background: Moyamoya disease (MMD) is an important cause of stroke in children and young adults in Asia. To date, diagnosis remains challenging due to varying clinical manifestations and unknown pathogenesis. The study aims to identify cerebrospinal fluid (CSF) exosomal microRNAs (exomiRs) that can serve as a novel diagnostic biomarker for diagnosis and assess its clinical applications. Methods: CSF samples were taken from 31 MMD patients and 31 healthy controls. Initial screening of miRNA expression was performed on samples pooled from MMD patients and controls using microarray and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic accuracy of the potential exosomal miRNAs was evaluated using receiver operating characteristic curve analyses in an independent patient cohort. The potential pathways regulated by the miRNAs was also determined using bioinformatics analysis. Results: The microarray results demonstrated that six exomiRs were dysregulated in the MMD patients compared to the controls. Using qRT-PCR, we validated four of the miRNAs (miR-3679-5p, miR-6165, miR-6760-5p, and miR-574-5p) as a biomarker for MMD diagnosis. The four exomiRs showed enhanced sensitivity (75%) and specificity (93.75%) in terms of differentiating MMD patients from healthy subjects [area under the curve (AUC) = 0.9453]. Pathway enrichment analysis for potential targets of six exomiRs identified proteins involved in cell adhesion and junction formation in the brain. Conclusions: We identified a novel and highly sensitive exomiRs signature for MMD detection and explored its potential targets using bioinformatics analysis.

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Section: Discussionmentioning

confidence: 93%

A Panel of Exosome-Derived miRNAs of Cerebrospinal Fluid for the Diagnosis of Moyamoya Disease

et al. 2020

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“…The formation of neurofibrillary tangles is regarded to be one of the important pathological characteristics of AD, which may be caused by the accumulation of Aβ25-35 (38). Thus, a cell model of AD was established by treating SH-SY5Y cells with Aβ25-35, and the concentration of 40 µm/l has been proved to be most efficient (28). The present results demonstrated a significant downregulation of miR-133b in SH-SY5Y cells treated with Aβ25-35.…”

Section: Discussionmentioning

confidence: 99%

“…When the cells reached 80-90% confluence, the cell suspension was sub-cultured on a scale of 1:3. For the Aβ group, cells were seeded into a 96-well plate at a density of 1x10 4 cells per well, and after culture for 24 h, medium supplemented with Aβ25-35 (40 µM/l; Sigma-Aldrich; Merck KGaA) was added and the cells were cultured for another 48 h (28). Prior to use, Aβ25-35 was dissolved in sterile physiological saline and incubated at 37˚C for one week to allow for fibril formation.…”

Section: Sample Collectionmentioning

confidence: 99%

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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“…MiR-214-3p negatively regulates the expression of ATG12 by targeting its 3′ UTR, inhibits autophagy, and reduces the levels of apoptosis in hippocampal neurons ( Zhang et al, 2016a ). Increased expression of miR-4487 decreases Aβ-induced apoptosis in neurons ( Hu et al, 2018 ). Furthermore, miR-98 reduces Aβ production, inhibits the Notch signaling pathway, and suppresses the apoptosis of hippocampal neurons, thereby promoting their survival ( Chen et al, 2019 ).…”

Section: Mirnas Are Crucial For the Onset And Pathological Progressiomentioning

confidence: 99%

MicroRNAs in Alzheimer’s Disease: Function and Potential Applications as Diagnostic Biomarkers

Wei

Wang

et al. 2020

Front. Mol. Neurosci.

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Alzheimer's disease (AD) is the most common form of dementia. Although the incidence of AD is high, the rates of diagnosis and treatment are relatively low. Moreover, effective means for the diagnosis and treatment of AD are still lacking. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play regulatory roles by targeting mRNAs. The expression of miRNAs is conserved, temporal, and tissue-specific. Impairment of microRNA function is closely related to AD pathogenesis, including the betaamyloid and tau hallmarks of AD, and there is evidence that the expression of some microRNAs differs significantly between healthy people and AD patients. These properties of miRNAs endow them with potential diagnostic and therapeutic value in the treatment of this debilitating disease. This review provides comprehensive information about the regulatory function of miRNAs in AD, as well as potential applications as diagnostic biomarkers.

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The emerging role of microRNA-4487/6845-3p in Alzheimer’s disease pathologies is induced by Aβ25–35 triggered in SH-SY5Y cell

Cited by 25 publications

References 35 publications

A Panel of Exosome-Derived miRNAs of Cerebrospinal Fluid for the Diagnosis of Moyamoya Disease

A Panel of Exosome-Derived miRNAs of Cerebrospinal Fluid for the Diagnosis of Moyamoya Disease

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

MicroRNAs in Alzheimer’s Disease: Function and Potential Applications as Diagnostic Biomarkers

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