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pmid:36468008

Bioinformatics-based study reveals that AP2M1 is regulated by the circRNA-miRNA-mRNA interaction network and affects Alzheimer's disease.

Qi Zhang · Bishuang Chen · Ping Yang · Jipan Wu · Xinping Pang · Chaoyang Pang

Frontiers in genetics · 2022 doi:10.3389/fgene.2022.1049786

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Data

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title
Bioinformatics-based study reveals that AP2M1 is regulated by the circRNA-miRNA-mRNA interaction network and affects Alzheimer's disease.
doi
10.3389/fgene.2022.1049786
pmid
36468008
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[0]
Qi Zhang
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Bishuang Chen
[2]
Ping Yang
[3]
Jipan Wu
[4]
Xinping Pang
[5]
Chaoyang Pang
journal
Frontiers in genetics
year
2022
abstract
Alzheimer's disease (AD) is a progressive neurological disease that worsens with time. The hallmark illnesses include extracellular senile plaques caused by β-amyloid protein deposition, neurofibrillary tangles caused by tau protein hyperphosphorylation, and neuronal loss accompanying glial cell hyperplasia. Noncoding RNAs are substantially implicated in related pathophysiology, according to mounting data. However, the function of these ncRNAs is mainly unclear. Circular RNAs (circRNAs) include many miRNA-binding sites (miRNA response elements, MREs), which operate as miRNA sponges or competing endogenous RNAs (ceRNAs). The purpose of this study was to look at the role of circular RNAs (circRNAs) and microRNAs (miRNAs) in Alzheimer's disease (AD) as possible biomarkers. The Gene Expression Omnibus (GEO) database was used to obtain an expression profile of Alzheimer's disease patients (GSE5281, GSE122603, GSE97760, GSE150693, GSE1297, and GSE161435). Through preliminary data deletion, 163 genes with significant differences, 156 miRNAs with significant differences, and 153 circRNAs with significant differences were identified. Then, 10 key genes, led by MAPT and AP2M1, were identified by the mediation center algorithm, 34 miRNAs with obvious prognosis were identified by the cox regression model, and 16 key circRNAs were selected by the database. To develop competitive endogenous RNA (ceRNA) networks, hub circRNAs and mRNAs were used. Finally, GO analysis and clinical data verification of key genes were carried out. We discovered that a down-regulated circRNA (has_circ_002048) caused the increased expression of numerous miRNAs, which further inhibited the expression of a critical mRNA (AP2M1), leading to Alzheimer's disease pathology. The findings of this work contribute to a better understanding of the circRNA-miRNA-mRNA regulating processes in Alzheimer's disease. Furthermore, the ncRNAs found here might become novel biomarkers and potential targets for the development of Alzheimer's drugs.
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Data were processed using DEG’s GEO2R online analysis tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/), and adjusted p-values and |logFC| were calculated. Differential miRNAs were screened and selected from GSE150693 by the ‘limma’ package in the ‘R' language based on the criteria of p < 0.05 and FC > 1.
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Data were processed using DEG’s GEO2R online analysis tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/), and adjusted p-values and |logFC| were calculated.
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sections[4] "Data processing of differentially expressed (DE) ncRNAs and DEGs" paragraph 2
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Differential miRNAs were screened and selected from GSE150693 by the ‘limma’ package in the ‘R' language based on the criteria of p < 0.05 and FC > 1.
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A down-regulated circRNA, has_circ_002048, increased numerous miRNAs that further inhibited AP2M1, leading to Alzheimer’s disease pathology.
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We discovered that a down-regulated circRNA (has_circ_002048) caused the increased expression of numerous miRNAs, which further inhibited the expression of a critical mRNA (AP2M1), leading to Alzheimer’s disease pathology.
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A down-regulated circRNA, has_circ_002048, increased numerous miRNAs that further inhibited AP2M1, leading to Alzheimer’s disease pathology.
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The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
access_statement_kind
data_availability_statement
sample_accessions array · 6 items
[0]
GSM4907314
[1]
GSM4907315
[2]
GSM4907316
[3]
GSM4907317
[4]
GSM4907318
[5]
GSM4907319
sample_count
6
group_sizes
null
group_sizes_basis
null
platform
21825
taxon
Homo sapiens
title
Identification of aberrant circRNAs in peripheral whole blood of patients with Alzheimer's disease
resolution_checked_at
2026-11-01T18:46:34Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[5] object · 15 fields
id
data:geo:GSE5281
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5281
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE5281
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
access_statement_kind
data_availability_statement
sample_accessions array · 161 items
[0]
GSM119615
[1]
GSM119616
[2]
GSM119617
[3]
GSM119618
[4]
GSM119619
[5]
GSM119620
[6]
GSM119621
[7]
GSM119622
[8]
GSM119623
[9]
GSM119624
[10]
GSM119625
[11]
GSM119626
[12]
GSM119627
[13]
GSM119628
[14]
GSM119629
[15]
GSM119630
[16]
GSM119631
[17]
GSM119632
[18]
GSM119633
[19]
GSM119634
[20]
GSM119635
[21]
GSM119636
[22]
GSM119637
[23]
GSM119638
[24]
GSM119639
[25]
GSM119640
[26]
GSM119641
[27]
GSM119642
[28]
GSM119643
[29]
GSM119644
[30]
GSM119645
[31]
GSM119646
[32]
GSM119647
[33]
GSM119648
[34]
GSM119649
[35]
GSM119650
[36]
GSM119651
[37]
GSM119652
[38]
GSM119653
[39]
GSM119654
[40]
GSM119655
[41]
GSM119656
[42]
GSM119657
[43]
GSM119658
[44]
GSM119659
[45]
GSM119660
[46]
GSM119661
[47]
GSM119662
[48]
GSM119663
[49]
GSM119664
[50]
GSM119665
[51]
GSM119666
[52]
GSM119667
[53]
GSM119668
[54]
GSM119669
[55]
GSM119670
[56]
GSM119671
[57]
GSM119672
[58]
GSM119673
[59]
GSM119674
[60]
GSM119675
[61]
GSM119676
[62]
GSM119677
[63]
GSM119678
[64]
GSM119679
[65]
GSM119680
[66]
GSM119681
[67]
GSM119682
[68]
GSM119683
[69]
GSM119684
[70]
GSM119685
[71]
GSM119686
[72]
GSM119687
[73]
GSM119688
[74]
GSM238763
[75]
GSM238790
[76]
GSM238791
[77]
GSM238792
[78]
GSM238793
[79]
GSM238794
[80]
GSM238795
[81]
GSM238796
[82]
GSM238797
[83]
GSM238798
[84]
GSM238799
[85]
GSM238800
[86]
GSM238801
[87]
GSM238802
[88]
GSM238803
[89]
GSM238804
[90]
GSM238805
[91]
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[92]
GSM238807
[93]
GSM238808
[94]
GSM238809
[95]
GSM238810
[96]
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[97]
GSM238812
[98]
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[99]
GSM238815
[100]
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[101]
GSM238817
[102]
GSM238818
[103]
GSM238819
[104]
GSM238820
[105]
GSM238821
[106]
GSM238822
[107]
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[108]
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[109]
GSM238825
[110]
GSM238826
[111]
GSM238827
[112]
GSM238834
[113]
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[114]
GSM238837
[115]
GSM238838
[116]
GSM238839
[117]
GSM238840
[118]
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[119]
GSM238842
[120]
GSM238843
[121]
GSM238844
[122]
GSM238845
[123]
GSM238846
[124]
GSM238847
[125]
GSM238848
[126]
GSM238851
[127]
GSM238854
[128]
GSM238855
[129]
GSM238856
[130]
GSM238857
[131]
GSM238858
[132]
GSM238860
[133]
GSM238861
[134]
GSM238862
[135]
GSM238863
[136]
GSM238864
[137]
GSM238865
[138]
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[139]
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[140]
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GSM238871
[142]
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[143]
GSM238873
[144]
GSM238874
[145]
GSM238875
[146]
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[150]
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GSM238949
[156]
GSM238951
[157]
GSM238952
[158]
GSM238953
[159]
GSM238955
[160]
GSM238963
sample_count
161
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Alzheimer's disease and the normal aged brain (steph-affy-human-433773)
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[6] object · 15 fields
id
data:geo:GSE97760
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97760
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE97760
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
access_statement_kind
data_availability_statement
sample_accessions array · 19 items
[0]
GSM2577046
[1]
GSM2577047
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GSM2577048
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GSM2577049
[4]
GSM2577050
[5]
GSM2577051
[6]
GSM2577052
[7]
GSM2577053
[8]
GSM2577054
[9]
GSM2577055
[10]
GSM2577056
[11]
GSM2577057
[12]
GSM2577058
[13]
GSM2577059
[14]
GSM2577060
[15]
GSM2577061
[16]
GSM2577062
[17]
GSM2577063
[18]
GSM2577064
sample_count
19
group_sizes
null
group_sizes_basis
null
platform
16699
taxon
Homo sapiens
title
Blood genome-wide gene expression microarray profiles in female patients with advanced Alzheimer's Disease and healthy controls
resolution_checked_at
2026-11-01T18:06:44Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 12 items
[0]
asset:data:geo:GSE122063 not downloaded
[1]
asset:data:geo:GSE122063 licence not read
[2]
asset:data:geo:GSE1297 not downloaded
[3]
asset:data:geo:GSE1297 licence not read
[4]
asset:data:geo:GSE150693 not downloaded
[5]
asset:data:geo:GSE150693 licence not read
[6]
asset:data:geo:GSE161435 not downloaded
[7]
asset:data:geo:GSE161435 licence not read
[8]
asset:data:geo:GSE5281 not downloaded
[9]
asset:data:geo:GSE5281 licence not read
[10]
asset:data:geo:GSE97760 not downloaded
[11]
asset:data:geo:GSE97760 licence not read
analysis object · 4 fields
state
complete
methods array · 5 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
1
band
reordered
quote
Data were processed using DEG’s GEO2R online analysis tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/), and adjusted p-values and |logFC| were calculated. Differential miRNAs were screened and selected from GSE150693 by the ‘limma’ package in the ‘R' language based on the criteria of p < 0.05 and FC > 1.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
missing_operations array · 0 items
parameters object · 1 field
p_value
d on the criteria of KM-Pvalue<0
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
KM
[2] object · 10 fields
id
method-3
family
survival_analysis
specific
log_rank_test
label
Survival analysis
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[0]
logrank_test
missing_operations array · 0 items
parameters object · 1 field
p_value
ed by using the minimum p-value of the log-rank test to
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
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log-rank
[3] object · 10 fields
id
method-4
family
differential_expression
specific
limma_voom
label
Differential expression analysis
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[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
0.8
band
high
quote
limma
[4] object · 10 fields
id
method-5
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.8
band
high
quote
pathway enrichment
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 6 items
[0]
GSE5281
[1]
GSE97760
[2]
GSE122063
[3]
GSE150693
[4]
GSE161435
[5]
GSE1297
resolved_accessions array · 6 items
[0]
GSE5281
[1]
GSE97760
[2]
GSE122063
[3]
GSE150693
[4]
GSE161435
[5]
GSE1297
statements array · 1 item
[0]
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
basis
The paper names GSE5281, GSE97760, GSE122063, GSE150693, GSE161435, GSE1297 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
cox_ph
assets array · 2 items
[0]
source:pmid:36468008
[1]
data:geo:GSE122063
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[0]
run_analysis
must_build object · 5 fields
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readers array · 0 items
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data_gaps array · 1 item
[0]
data:geo:GSE122063
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review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T18:18:25Z
independence
single_reader
evidence_check object · 2 fields
method
reordered
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
12006
completion_tokens
2695
cached_tokens
256
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
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null
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
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id
pmid:36468008
type
paper
label
pmid:36468008
[1] object · 3 fields
id
source:pmid:36468008
type
manuscript
label
PMID 36468008 full text
[2] object · 3 fields
id
data:geo:GSE122063
type
dataset
label
GEO GSE122063
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:36468008
type
paper
label
pmid:36468008
[1] object · 3 fields
id
source:pmid:36468008
type
manuscript
label
PMID 36468008 full text
[2] object · 3 fields
id
data:geo:GSE122063
type
dataset
label
GEO GSE122063
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-36468008
type
extraction
used array · 1 item
[0]
source:pmid:36468008
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE122063
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accession_resolution
used array · 1 item
[0]
data:geo:GSE122063
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agent:corpus-assay-engine
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[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
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Corpus assay engine
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id
agent:minimax-reader
type
software
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MiniMax literature reader
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reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:36468008
parent_hash
sha256:b7781a95f287ee7d742b66cf7f95dced450714b84dd520095be6a9df35f515ed
fork_of
null
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[0]
asset:data:geo:GSE122063 licence not read
[1]
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[2]
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[3]
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[4]
asset:data:geo:GSE150693 licence not read
[5]
asset:data:geo:GSE150693 not downloaded
[6]
asset:data:geo:GSE161435 licence not read
[7]
asset:data:geo:GSE161435 not downloaded
[8]
asset:data:geo:GSE5281 licence not read
[9]
asset:data:geo:GSE5281 not downloaded
[10]
asset:data:geo:GSE97760 licence not read
[11]
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[12]
execution.not_run
[13]
review.human_critique
[14]
review.independent_reader
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assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
survival_analysis
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f2132e96ae6c7a4e
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cox_ph
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supported
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dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Data were processed using DEG’s GEO2R online analysis tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/), and adjusted p-values and |logFC| were calculated. Differential miRNAs were screened and selected from GSE150693 by the ‘limma’ package in the ‘R' language based on the criteria of p < 0.05 and FC > 1.
order_basis
analysis_only
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36468008", "kind": "science-record", "revision": 4, "content_hash": "sha256:54da83a243f150efe95cf39bd24ff4a9dc69a860531822e6efde55491a37c6ba", "created_at": "2026-11-01T19:00:57Z", "updated_at": "2026-11-01T22:50:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics-based study reveals that AP2M1 is regulated by the circRNA-miRNA-mRNA interaction network and affects Alzheimer's disease.", "doi": "10.3389/fgene.2022.1049786", "pmid": "36468008", "authors": ["Qi Zhang", "Bishuang Chen", "Ping Yang", "Jipan Wu", "Xinping Pang", "Chaoyang Pang"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Alzheimer's disease (AD) is a progressive neurological disease that worsens with time. The hallmark illnesses include extracellular senile plaques caused by β-amyloid protein deposition, neurofibrillary tangles caused by tau protein hyperphosphorylation, and neuronal loss accompanying glial cell hyperplasia. Noncoding RNAs are substantially implicated in related pathophysiology, according to mounting data. However, the function of these ncRNAs is mainly unclear. Circular RNAs (circRNAs) include many miRNA-binding sites (miRNA response elements, MREs), which operate as miRNA sponges or competing endogenous RNAs (ceRNAs). The purpose of this study was to look at the role of circular RNAs (circRNAs) and microRNAs (miRNAs) in Alzheimer's disease (AD) as possible biomarkers. The Gene Expression Omnibus (GEO) database was used to obtain an expression profile of Alzheimer's disease patients (GSE5281, GSE122603, GSE97760, GSE150693, GSE1297, and GSE161435). Through preliminary data deletion, 163 genes with significant differences, 156 miRNAs with significant differences, and 153 circRNAs with significant differences were identified. Then, 10 key genes, led by MAPT and AP2M1, were identified by the mediation center algorithm, 34 miRNAs with obvious prognosis were identified by the cox regression model, and 16 key circRNAs were selected by the database. To develop competitive endogenous RNA (ceRNA) networks, hub circRNAs and mRNAs were used. Finally, GO analysis and clinical data verification of key genes were carried out. We discovered that a down-regulated circRNA (has_circ_002048) caused the increased expression of numerous miRNAs, which further inhibited the expression of a critical mRNA (AP2M1), leading to Alzheimer's disease pathology. The findings of this work contribute to a better understanding of the circRNA-miRNA-mRNA regulating processes in Alzheimer's disease. 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