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pmid:30816541

Reconstruction and analysis of circRNA‑miRNA‑mRNA network in the pathology of cervical cancer.

Yuexiong Yi · Yanyan Liu · Wanrong Wu · Kejia Wu · Wei Zhang

Oncology reports · 2019 doi:10.3892/or.2019.7028

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Experiment

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title
Reconstruction and analysis of circRNA‑miRNA‑mRNA network in the pathology of cervical cancer.
doi
10.3892/or.2019.7028
pmid
30816541
authors array · 5 items
[0]
Yuexiong Yi
[1]
Yanyan Liu
[2]
Wanrong Wu
[3]
Kejia Wu
[4]
Wei Zhang
journal
Oncology reports
year
2019
abstract
The present study was performed with the aim of understanding the mechanisms of pathogenesis and providing novel biomarkers for cervical cancer by constructing a regulatory circular (circ)RNA‑micro (mi)RNA‑mRNA network. Using an adjusted P-value of <0.05 and an absolute log value of fold-change >1, 16 and 156 miRNAs from GSE30656 and The Cancer Genome Atlas (TCGA), 5,321 mRNAs from GSE63514, 4,076 mRNAs from cervical squamous cell carcinoma and endocervical adenocarcinoma (from TCGA) and 75 circRNAs from GSE102686 were obtained. Using RNAhybrid, Venn and UpSetR plot, 12 circRNA‑miRNA pairs and 266 miRNA‑mRNA pairs were obtained. Once these pairs were combined, a circRNA‑miRNA‑mRNA network with 11 circRNA nodes, 4 miRNA nodes, 153 mRNA nodes and 203 edges was constructed. By constructing the protein‑protein interaction network using Molecular Complex Detection scores >5 and >5 nodes, 7 hubgenes (RRM2, CEP55, CHEK1, KIF23, RACGAP1, ATAD2 and KIF11) were identified. By mapping the 7 hubgenes into the preliminary circRNA‑miRNA‑mRNA network, a circRNA‑miRNA‑hubgenes network consisting of 5 circRNAs (hsa_circRNA_000596, hsa_circRNA_104315, hsa_circRNA_400068, hsa_circRNA_101958 and hsa_circRNA_103519), 2 mRNAs (hsa‑miR‑15b and hsa‑miR‑106b) and 7 mRNAs (RRM2, CEP55, CHEK1, KIF23, RACGAP1, ATAD2 and KIF11) was constructed. There were 22 circRNA‑miRNA‑mRNA regulatory axes identified in the subnetwork. By analyzing the overall survival for the 7 hubgenes using the Gene Expression Profiling Interactive Analysis tool, higher expression of RRM2 was demonstrated to be associated with a significantly poorer overall survival. PharmGkb analysis identified single nucleotide polymorphisms (SNPs) of rs5030743 and rs1130609 of RRM2, which can be treated with cladribine and cytarabine. RRM2 was also indicated to be involved in the gemcitabine pathway. The 5 circRNAs (hsa_circRNA_000596, hsa_circRNA_104315, hsa_circRNA_400068, hsa_circRNA_101958 and hsa_circRNA_103519) may function as competing endogenous RNAs and serve critical roles in cervical cancer. In addition, cytarabine may produce similar effects to gemcitabine and may be an optional chemotherapeutic drug for treating cervical cancer by targeting rs5030743 and rs1130609 or other similar SNPs. However, the specific mechanism of action should be confirmed by further study.
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The adjusted P-value (adj.p) and the absolute log value of fold-change (log|FC|) were calculated using R software with limma package (25).
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sections[5] "Identification of differentially expressed (DE)-miRNAs, DE-circRNAs and DE-mRNAs" paragraph 2
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The adjusted P-value (adj.p) and the absolute log value of fold-change (log|FC|) were calculated using R software with limma package (25).
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Gene expression analysis of cervical cancer progression
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Regulatory axis identified from the circRNA-miRNA-hubgene network.
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Table II.
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Regulatory axis identified from the circRNA-miRNA-hubgene network.
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Primary characteristics of the 5 circRNAs identified from the circRNA-miRNA-hubgene network.
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Construction of the circRNA-miRNA-hubgenes network
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Table III.
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Primary characteristics of the 5 circRNAs identified from the circRNA-miRNA-hubgene network.
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[4]
Strand
[5]
Location
[6]
Gene symbol
[7]
Regulation
[1] array · 8 items
[0]
hsa_circRNA_000596
[1]
Chr15
[2]
100589061
[3]
100739628
[4]
+
[5]
Exon
[6]
ADAMTS17
[7]
Upregulated
[2] array · 8 items
[0]
hsa_circRNA_400068
[1]
Chr22
[2]
20109884
[3]
20114047
[4]
+
[5]
Exon
[6]
RANBP1
[7]
Downregulated
[3] array · 8 items
[0]
hsa_circRNA_104315
[1]
Chr7
[2]
16298014
[3]
16330476
[4]
−
[5]
Exon
[6]
ISPD
[7]
Downregulated
[4] array · 8 items
[0]
hsa_circRNA_101958
[1]
Chr17
[2]
4192524
[3]
4207021
[4]
−
[5]
Exon
[6]
UBE2G1
[7]
Downregulated
[5] array · 8 items
[0]
hsa_circRNA_103519
[1]
Chr3
[2]
179042885
[3]
179051613
[4]
+
[5]
Exon
[6]
ZNF639
[7]
Upregulated
locator
section[21]/table-wrap[2]#tIII-or-41-04-2209
[7] object · 16 fields
id
asset:table:pmid:30816541:4
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table
format
jats-table
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application/vnd.jats.table+json
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null
sha256
sha256:8929026324d2ab0e170f0db37fc07a391f238301203af5eff4068fc36a91f158
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933
access
open
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verified
reader
read_table
reader_status
available
identifier
section[24]/table-wrap[1]#tIV-or-41-04-2209
version
null
note
Information of SNPs and clinical data for RRM2.
structure object · 5 fields
pmcid
PMC6412533
section_index
24
section_title
Pharmacogenomics analysis for RRM2
row_count
3
column_count
9
table object · 8 fields
label
Table IV.
caption
Information of SNPs and clinical data for RRM2.
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[0] array · 9 items
[0]
Genes
[1]
SNP
[2]
Drug
[3]
Efficiency
[4]
Significant
[5]
P-value
[6]
Association
[7]
Reference
[8]
Pathways
[1] array · 9 items
[0]
RRM2
[1]
rs5030743
[2]
Cladribine; Cytarabine
[3]
Effective
[4]
Yes
[5]
0.013
[6]
Genotypes CG + GG is associated with decreased response to cladribine and cytarabine in children with leukemia, myeloid, acute as compared to genotype CC
[7]
PMID: 24024897
[8]
Thiopurine pathway; Fluoropyrimidine pathway; Gemcitabine pathway
[2] array · 9 items
[0]
RRM2
[1]
rs1130609
[2]
Cladribine; Cytarabine
[3]
Efficacy
[4]
Yes
[5]
0.020
[6]
Genotypes GT + TT is associated with decreased response to cladribine and cytarabine in children with leukemia, myeloid, acute as compared to genotype GG
[7]
PMID: 24024897
[8]
Thiopurine pathway; Fluoropyrimidine pathway; Gemcitabine pathway
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section[24]/table-wrap[1]#tIV-or-41-04-2209
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[0]
asset:data:geo:GSE102686 not downloaded
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asset:data:geo:GSE102686 licence not read
[2]
asset:data:geo:GSE30656 not downloaded
[3]
asset:data:geo:GSE30656 licence not read
[4]
asset:data:geo:GSE63514 not downloaded
[5]
asset:data:geo:GSE63514 licence not read
analysis object · 4 fields
state
complete
methods array · 1 item
[0] object · 10 fields
id
method-1
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
1
band
verbatim
quote
The adjusted P-value (adj.p) and the absolute log value of fold-change (log|FC|) were calculated using R software with limma package (25).
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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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: limma_voom.
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 · 3 items
[0]
GSE102686
[1]
GSE30656
[2]
GSE63514
resolved_accessions array · 3 items
[0]
GSE102686
[1]
GSE30656
[2]
GSE63514
statements array · 1 item
[0]
All data generated or analyzed during this study are included in this published article.
basis
The paper names GSE102686, GSE30656, GSE63514 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 · 3 items
[0]
normalise_counts
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differential_expression_fit
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fdr_bh
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[0]
source:pmid:30816541
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data:geo:GSE102686
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asset:table:pmid:30816541:1
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asset:table:pmid:30816541:2
[4]
asset:table:pmid:30816541:3
[5]
asset:table:pmid:30816541:4
steps array · 1 item
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run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
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readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
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data:geo:GSE102686
gaps array · 0 items
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
2026-10-31T18:14:03Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
46694
completion_tokens
1708
cached_tokens
784
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
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review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
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gaps array · 1 item
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execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:30816541
type
paper
label
pmid:30816541
[1] object · 3 fields
id
source:pmid:30816541
type
manuscript
label
PMID 30816541 full text
[2] object · 3 fields
id
data:geo:GSE102686
type
dataset
label
GEO GSE102686
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:30816541
type
paper
label
pmid:30816541
[1] object · 3 fields
id
source:pmid:30816541
type
manuscript
label
PMID 30816541 full text
[2] object · 3 fields
id
data:geo:GSE102686
type
dataset
label
GEO GSE102686
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-30816541
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extraction
used array · 1 item
[0]
source:pmid:30816541
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE102686
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accession_resolution
used array · 1 item
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data:geo:GSE102686
agent
agent:corpus-assay-engine
agents array · 2 items
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id
agent:corpus-assay-engine
type
software
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Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
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software
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MiniMax literature reader
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343fb30756ba6ec3
capability_table_fingerprint
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ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:30816541
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fork_of
null
gaps array · 10 items
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asset:data:geo:GSE102686 licence not read
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asset:data:geo:GSE30656 licence not read
[3]
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[5]
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execution.not_run
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review.human_critique
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assays array · 1 item
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role
analysis
definition_id
differential_expression
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normalise_counts
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differential_expression_fit
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fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
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The adjusted P-value (adj.p) and the absolute log value of fold-change (log|FC|) were calculated using R software with limma package (25).
order_basis
analysis_only
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assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30816541", "kind": "science-record", "revision": 8, "content_hash": "sha256:d19a713eb4652c3f60c17da60a610bcbe3bac2a753c9c0ae6cc91ec961557fcf", "created_at": "2026-11-01T15:40:42Z", "updated_at": "2026-11-01T22:43:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Reconstruction and analysis of circRNA‑miRNA‑mRNA network in the pathology of cervical cancer.", "doi": "10.3892/or.2019.7028", "pmid": "30816541", "authors": ["Yuexiong Yi", "Yanyan Liu", "Wanrong Wu", "Kejia Wu", "Wei Zhang"], "journal": "Oncology reports", "year": 2019, "abstract": "The present study was performed with the aim of understanding the mechanisms of pathogenesis and providing novel biomarkers for cervical cancer by constructing a regulatory circular (circ)RNA‑micro (mi)RNA‑mRNA network. Using an adjusted P-value of <0.05 and an absolute log value of fold-change >1, 16 and 156 miRNAs from GSE30656 and The Cancer Genome Atlas (TCGA), 5,321 mRNAs from GSE63514, 4,076 mRNAs from cervical squamous cell carcinoma and endocervical adenocarcinoma (from TCGA) and 75 circRNAs from GSE102686 were obtained. Using RNAhybrid, Venn and UpSetR plot, 12 circRNA‑miRNA pairs and 266 miRNA‑mRNA pairs were obtained. Once these pairs were combined, a circRNA‑miRNA‑mRNA network with 11 circRNA nodes, 4 miRNA nodes, 153 mRNA nodes and 203 edges was constructed. By constructing the protein‑protein interaction network using Molecular Complex Detection scores >5 and >5 nodes, 7 hubgenes (RRM2, CEP55, CHEK1, KIF23, RACGAP1, ATAD2 and KIF11) were identified. By mapping the 7 hubgenes into the preliminary circRNA‑miRNA‑mRNA network, a circRNA‑miRNA‑hubgenes network consisting of 5 circRNAs (hsa_circRNA_000596, hsa_circRNA_104315, hsa_circRNA_400068, hsa_circRNA_101958 and hsa_circRNA_103519), 2 mRNAs (hsa‑miR‑15b and hsa‑miR‑106b) and 7 mRNAs (RRM2, CEP55, CHEK1, KIF23, RACGAP1, ATAD2 and KIF11) was constructed. There were 22 circRNA‑miRNA‑mRNA regulatory axes identified in the subnetwork. By analyzing the overall survival for the 7 hubgenes using the Gene Expression Profiling Interactive Analysis tool, higher expression of RRM2 was demonstrated to be associated with a significantly poorer overall survival. PharmGkb analysis identified single nucleotide polymorphisms (SNPs) of rs5030743 and rs1130609 of RRM2, which can be treated with cladribine and cytarabine. RRM2 was also indicated to be involved in the gemcitabine pathway. The 5 circRNAs (hsa_circRNA_000596, hsa_circRNA_104315, hsa_circRNA_400068, hsa_circRNA_101958 and hsa_circRNA_103519) may function as competing endogenous RNAs and serve critical roles in cervical cancer. In addition, cytarabine may produce similar effects to gemcitabine and may be an optional chemotherapeutic drug for treating cervical cancer by targeting rs5030743 and rs1130609 or other similar SNPs. However, the specific mechanism of action should be confirmed by further study.", "claims": [{"id": "claim-method", "statement": "The adjusted P-value (adj.p) and the absolute log value of fold-change (log|FC|) were calculated using R software with limma package (25).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30816541", "locator": "sections[5] \"Identification of differentially expressed (DE)-miRNAs, DE-circRNAs and DE-mRNAs\" paragraph 2", "quote": "The adjusted P-value (adj.p) and the absolute log value of fold-change (log|FC|) were calculated using R software with limma package (25)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30816541", "locator": "sections[28] \"Availability of data and materials\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this published article."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30816541"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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