Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer’s disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01-31

AUTHORS

Norikazu Hara, Masataka Kikuchi, Akinori Miyashita, Hiroyuki Hatsuta, Yuko Saito, Kensaku Kasuga, Shigeo Murayama, Takeshi Ikeuchi, Ryozo Kuwano

ABSTRACT

MicroRNAs (miRNAs) are attractive molecules to utilize as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer’s disease (AD) because miRNAs are relatively stable in biofluid, including serum or plasma. To determine blood miRNA biomarkers for AD with next-generation sequencing genome-wide, we first surveyed 45 serum samples. These came from 27 AD patients and 18 controls (discovery set) that underwent autopsy within two weeks after their serum sampling and were neuropathologically diagnosed. We found that three miRNAs, hsa-miR-501-3p, hsa-let-7f-5p, and hsa-miR-26b-5p, were significantly deregulated between the AD samples and the controls. The deregulation for hsa-miR-501-3p was further confirmed by quantitative reverse transcription polymerase chain reaction (PCR) in a validation set composed of 36 clinically diagnosed AD patients and 22 age-matched cognitively normal controls with a sensitivity and specificity of 53% and 100%, respectively (area under the curve = 0.82). Serum hsa-miR-501-3p levels were downregulated in AD patients, and its lower levels significantly correlated with lower Mini-Mental State Examination scores. Contrary to its serum levels, we found that hsa-miR-501-3p was remarkably upregulated in the same donors’ AD brains obtained at autopsy from the discovery set. The hsa-miR-501-3p overexpression in cultured cells, which mimicked the hsa-miR-501-3p upregulation in the AD brains, induced significant downregulation of 128 genes that overrepresented the Gene Ontology terms, DNA replication, and the mitotic cell cycle. Our results suggest that hsa-miR-501-3p is a novel serum biomarker that presumably corresponds to pathological events occurring in AD brains. More... »

PAGES

10

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40478-017-0414-z

DOI

http://dx.doi.org/10.1186/s40478-017-0414-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1083395141

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28137310


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34 schema:description MicroRNAs (miRNAs) are attractive molecules to utilize as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer’s disease (AD) because miRNAs are relatively stable in biofluid, including serum or plasma. To determine blood miRNA biomarkers for AD with next-generation sequencing genome-wide, we first surveyed 45 serum samples. These came from 27 AD patients and 18 controls (discovery set) that underwent autopsy within two weeks after their serum sampling and were neuropathologically diagnosed. We found that three miRNAs, hsa-miR-501-3p, hsa-let-7f-5p, and hsa-miR-26b-5p, were significantly deregulated between the AD samples and the controls. The deregulation for hsa-miR-501-3p was further confirmed by quantitative reverse transcription polymerase chain reaction (PCR) in a validation set composed of 36 clinically diagnosed AD patients and 22 age-matched cognitively normal controls with a sensitivity and specificity of 53% and 100%, respectively (area under the curve = 0.82). Serum hsa-miR-501-3p levels were downregulated in AD patients, and its lower levels significantly correlated with lower Mini-Mental State Examination scores. Contrary to its serum levels, we found that hsa-miR-501-3p was remarkably upregulated in the same donors’ AD brains obtained at autopsy from the discovery set. The hsa-miR-501-3p overexpression in cultured cells, which mimicked the hsa-miR-501-3p upregulation in the AD brains, induced significant downregulation of 128 genes that overrepresented the Gene Ontology terms, DNA replication, and the mitotic cell cycle. Our results suggest that hsa-miR-501-3p is a novel serum biomarker that presumably corresponds to pathological events occurring in AD brains.
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41 AD patients
42 AD samples
43 Alzheimer's disease
44 DNA replication
45 Gene Ontology terms
46 HSA
47 Mini-Mental State Examination score
48 State Examination score
49 attractive molecule
50 biofluids
51 biomarkers
52 blood-based biomarkers
53 brain
54 cell cycle
55 cells
56 chain reaction
57 control
58 cultured cells
59 cycle
60 deregulation
61 discovery set
62 disease
63 disorders
64 donors
65 downregulation
66 events
67 examination scores
68 genes
69 genome
70 levels
71 low levels
72 lower Mini-Mental State Examination scores
73 miRNA biomarkers
74 miRNAs
75 microRNAs
76 mitotic cell cycle
77 molecules
78 neurodegenerative disorders
79 normal controls
80 novel serum biomarkers
81 ontology terms
82 overexpression
83 pathological events
84 patients
85 plasma
86 polymerase chain reaction
87 potential biomarkers
88 progression
89 quantitative reverse transcription polymerase chain reaction
90 reaction
91 replication
92 results
93 reverse transcription-polymerase chain reaction
94 same donor
95 samples
96 sampling
97 scores
98 sensitivity
99 sequencing genomes
100 serum
101 serum biomarkers
102 serum levels
103 serum microRNAs
104 serum samples
105 serum sampling
106 set
107 significant downregulation
108 specificity
109 terms
110 transcription-polymerase chain reaction
111 upregulation
112 validation set
113 weeks
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