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pmid:33552119

Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression.

Jing Yang · Chaoqin Chen · Xiaoyuan Jin · Lu Liu · Jiajia Lin · Xianhui Kang · Shengmei Zhu

Frontiers in genetics · 2020 doi:10.3389/fgene.2020.589370

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33552119
kind
science-record
content_hash
sha256:c5bfad758427c6f2232f11a30652eb1c292188ec9ee12fedba244540f4a20bb7
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https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T15:41:24Z
updated_at
2026-11-01T22:03:03Z
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paper object · 10 fields
state
complete
title
Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression.
doi
10.3389/fgene.2020.589370
pmid
33552119
authors array · 7 items
[0]
Jing Yang
[1]
Chaoqin Chen
[2]
Xiaoyuan Jin
[3]
Lu Liu
[4]
Jiajia Lin
[5]
Xianhui Kang
[6]
Shengmei Zhu
journal
Frontiers in genetics
year
2020
abstract
BACKGROUND: Depression is a prevalent mental disorder, which is difficult to diagnose and treat due to its unclear pathogenic mechanisms. The discovery of novel and effective therapeutic targets for depression is urgently needed. The hippocampus is a crucial region involved in depression and has been a therapeutic target for many antidepressants. Thus, it is beneficial for comprehensive research to be carried out on the molecular mechanisms of the hippocampus involved in the pathogenesis of depression. This study aims to investigate the differentially expressed genes (DEG) in the hippocampus in a chronic unpredictable mild stress (CUMS) mouse model. METHOD: The study obtained GSE84183 from the GEO database. The R language screened the differential expression genes (DEG) in the hippocampus tissue of depressed mice, and the enrichment pathways of DEGs were analyzed. A protein-protein interaction (PPI) network was constructed in the STRING database and visualized in Cytoscape software. MicroRNAs for these DEGs were obtained from TarBase and mortar base databases, and transcription factors (TF) related to DEG were predicted from the ENCODE database. Both networks used the visual analysis platform NetworkAnalyst. Finally, the microRNA-TF network was integrated based on the above two networks and imported into Cytoscape for further analysis. RESULTS: This study screened 325 differentially expressed genes, containing 42 downregulated genes and 283 upregulated genes. Most of these genes are enriched in the cell cycle and the chemokine signaling pathway. Meanwhile, Wfs1, one of the top ten DEGs, was identified as the key regulator of the cell cycle and the participator in the highest number of modules screened out in PPI networks. Wfs1-related molecules, including UBTF, mmu-mir-17-5p, and mmu-mir-7b-5p, were therefore screened out. Furthermore, we confirmed the downregulation of Wfs1 and upregulation of UBTF/mmu-mir-17-5p/mmu-mir-7b-5p in the hippocampus of the CUMS mouse model. Our data indicate that Wfs1 and related molecules were predicted to be associated with the pathological process of depression. This research provided potential new molecular targets of stress-induced depression.
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Students’ t-test tests were used for analyzing statistic differences, as indicated in Figure legends.
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sections[13] "Data and Statistical Analysis" paragraph 2
quote
Students’ t-test tests were used for analyzing statistic differences, as indicated in Figure legends.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
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sections[23] "Data Availability Statement" paragraph 2
quote
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
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Apply the paper's statistical method to the resolved series and compare the result with the published target.
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title
Transcription profiling of dentate gyrus and anterior cingulate cortex in mice exposed Unpredicatble Chronic Mild Stress and treated with fluoxetine
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Primer used in this study.
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PMC7863986
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12
section_title
Real-Time Polymerase Chain Reaction (RT-PCR)
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13
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TABLE 1
caption
Primer used in this study.
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[0] array · 3 items
[0]
Gene
[1]
Primers
[2]
Sequence
[1] array · 3 items
[0]
GAPDH
[1]
Forward primers
[2]
AAGGTCGGTGTGAACGGATT
[2] array · 3 items
[0]
[1]
Reverse primers
[2]
TGAACTTGCCGTGGGTAGAG
[3] array · 3 items
[0]
Wfs1
[1]
Forward primers
[2]
GGAAACTAACATGGCCCGGA
[4] array · 3 items
[0]
[1]
Reverse primers
[2]
GTGATGGAGGGTCTTTGGGG
[5] array · 3 items
[0]
UBTF
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Forward primers
[2]
ACAACCTCCCATCCAACGAC
[6] array · 3 items
[0]
[1]
Reverse primers
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TGTTGTGTTGACCCCTCCAC
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Forward primers
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AGAGAAGATTAGCATGGCCCCTG
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[1]
Reverse primers
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ATCCAGTGCAGGGTCCGAGG
[9] array · 3 items
[0]
mmu-mir-17-5p
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Forward primers
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ACACTCCAGCTGGGCAAAGTGCTTACAGTGCAG
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[0]
[1]
Reverse primers
[2]
CTCAACTGGTGTCGTGGA
[11] array · 3 items
[0]
mmu-mir-7b-5p
[1]
Forward primers
[2]
TCCAAGACATGTGATCCGTGTT
[12] array · 3 items
[0]
[1]
Reverse primers
[2]
GGGTTACTCCCGTTTGGTTGT
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section[12]/table-wrap[1]#T1
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Top 10 biological process of DEGs.
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PMC7863986
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17
section_title
Functional Enrichment Analysis of DEGs
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TABLE 2
caption
Top 10 biological process of DEGs.
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[0] array · 3 items
[0]
Term
[1]
Genes
[2]
P value
[1] array · 3 items
[0]
GO: 0050795 ∼ circadian rhythm
[1]
Lepr/Ptger3/Mc3r/Ghsr/Pmch/Ptgds/Casp1/Cckbr
[2]
9.60E-06
[2] array · 3 items
[0]
GO: 0007622 ∼ cytokine biosynthesis processes
[1]
Lepr/Chat/Ptger3/Mc3r/Pmch/Ptgds/Casp1
[2]
5.17E-06
[3] array · 3 items
[0]
GO: 0061053 ∼ prostaglandin biosynthesis processes
[1]
Gdf3/Frzb/Ror2/Foxc2/Dmrt2/Cobl/Aldh1a2
[2]
7.71E-05
[4] array · 3 items
[0]
GO: 0048592 ∼ synaptic vesicle fusion on the regulation of presynaptic active zone membrane
[1]
Kdr/Vax2/Hcn1/Trpm1/Rs1/Prox1/Rbp4/Nrl/Col8a2
[2]
0.000130269
[5] array · 3 items
[0]
GO:0030335∼segmentation
[1]
Gdf3/Sema3a/Ror2/Foxc2/Dmrt2/Cobl/Aldh1a2
[2]
7.88E-13
[6] array · 3 items
[0]
GO: 0048512 ∼circadian behavior
[1]
Lepr/Ptger3/Mc3r/Pmch/Ptgds/Casp1
[2]
5.02E-05
[7] array · 3 items
[0]
GO: 0048520 ∼positive regulation of behavior
[1]
Ptger3/Ghsr/Pmch/Casp1/Cckbr
[2]
6.79E-05
[8] array · 3 items
[0]
GO:0045087∼ positive regulation of sprouting angiogenesis
[1]
Kdr/Srpx2/Ghsr/Foxc2/Fgfbp1
[2]
2.01E-09
[9] array · 3 items
[0]
GO: 0051764 ∼actin crosslink formation
[1]
Baiap2l2/Tnnt2/Baiap2l1/Cobl
[2]
4.11E-06
[10] array · 3 items
[0]
GO: 0090050 positive regulation of cell migration involved in sprouting angiogenesis
[1]
Kdr/Srpx2/Foxc2/Fgfbp1
[2]
6.85E-05
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section[17]/table-wrap[1]#T2
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Module analysis of DEGs using Cytoscape.
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pmcid
PMC7863986
section_index
18
section_title
PPI Network and Module Analysis
row_count
10
column_count
5
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TABLE 3
caption
Module analysis of DEGs using Cytoscape.
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[0] array · 5 items
[0]
Cluster
[1]
Score
[2]
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[3]
Edges
[4]
Node IDs
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[0]
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[1]
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[2]
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[3]
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[4]
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[1]
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[4]
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[1]
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[4]
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Co-DEGs regulated by TF and miRNAs.
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pmcid
PMC7863986
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19
section_title
Construction of the TF-DEG- MicroRNA Network Analysis
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21
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6
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TABLE 4
caption
Co-DEGs regulated by TF and miRNAs.
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[0] array · 6 items
[0]
TF
[1]
DEGs
[2]
Gene counts
[3]
miRNA
[4]
DEGs
[5]
Gene counts
[1] array · 6 items
[0]
UBTF
[1]
Arid4b, Aff4, Raver1, Wfs1, Dtl, Camk2n1
[2]
6
[3]
mmu-mir-17-5p
[4]
Wfs1, Camk2n1, Aff4
[5]
3
[2] array · 6 items
[0]
ELF1
[1]
Aff4, Utf1, Raver1, Wfs1, Ckap4
[2]
5
[3]
mmu-let-7b-5p
[4]
Ptgds, Khsrp, Arhgap1
[5]
3
[3] array · 6 items
[0]
CHD2
[1]
Arhgap1, Khsrp, Dtl, Lin28a, Sall4
[2]
5
[3]
mmu-mir-362-3p
[4]
Lin28a, Wfs1, Igf1
[5]
3
[4] array · 6 items
[0]
HCFC1
[1]
Prox1, Raver1, Aff4, Ror2, Cbln1
[2]
5
[3]
mmu-mir-329-3p
[4]
Lin28a, Wfs1, Igf1
[5]
3
[5] array · 6 items
[0]
TBP
[1]
Aff4, Raver1, Wfs1, Dtl
[2]
4
[3]
mmu-mir-3473c
[4]
Camk2n1, Ror2, Shc4
[5]
3
[6] array · 6 items
[0]
MXI1
[1]
Utf1, Raver1, Ckap4, Khsrp
[2]
4
[3]
mmu-mir-7b-5p
[4]
Camk2n1, Raver1, Ubr2
[5]
3
[7] array · 6 items
[0]
MAZ
[1]
Raver1, Wfs1, Ckap4
[2]
3
[3]
mmu-mir-19b-3p
[4]
Arid4b, Camk2n1, Aff4
[5]
3
[8] array · 6 items
[0]
E2F4
[1]
Wfs1, Dtl, Khsrp
[2]
3
[3]
mmu-mir-340-5p
[4]
Arid4b, Camk2n1, Aff4
[5]
3
[9] array · 6 items
[0]
BHLHE40
[1]
Ckap4, Utf1, Shc4
[2]
3
[3]
mmu-mir-30e-5p
[4]
Arid4b, Camk2n1, Aff4
[5]
3
[10] array · 6 items
[0]
ETS1
[1]
Igf1, Dtl, Raver1
[2]
3
[3]
mmu-mir-466f-3p
[4]
Wfs1, Arid4b
[5]
2
[11] array · 6 items
[0]
USF1
[1]
Khsrp, Ptgds, Nrl
[2]
3
[3]
mmu-mir-466i-3p
[4]
Wfs1, Igf1
[5]
2
[12] array · 6 items
[0]
SIN3A
[1]
E2F4, Igf1, Dtl
[2]
3
[3]
mmu-let-7c-5p
[4]
Sall4, Lin28a
[5]
2
[13] array · 6 items
[0]
TCF12
[1]
Aff4, TCF12
[2]
2
[3]
mmu-mir-124-3p
[4]
Cbln1, Prox1
[5]
2
[14] array · 6 items
[0]
MYC
[1]
Utf1, Raver1
[2]
2
[3]
mmu-mir-26a-5p
[4]
Shc4, Ckap4
[5]
2
[15] array · 6 items
[0]
MYB
[1]
Utf1, Raver1
[2]
2
[3]
mmu-mir-9-5p
[4]
Ptgds, Ror2
[5]
2
[16] array · 6 items
[0]
ZMIZ1
[1]
Utf1, Raver1
[2]
2
[3]
mmu-mir-181a-5p
[4]
Aff4, Prox1
[5]
2
[17] array · 6 items
[0]
MEF2A
[1]
Ubr2, Shc4
[2]
2
[3]
mmu-mir-758-3p
[4]
Khsrp, Arid4b
[5]
2
[18] array · 6 items
[0]
KAT2A
[1]
Dtl, Raver1
[2]
2
[3]
mmu-mir-15a-5p
[4]
Igf1, Cbln1
[5]
2
[19] array · 6 items
[0]
GATA1
[1]
Raver1, Aff4
[2]
2
[3]
mmu-mir-149-5p
[4]
Cbln1, Arid4b
[5]
2
[20] array · 6 items
[0]
RCOR1
[1]
Raver1, Dtl
[2]
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n a chronic unpredictable mild stress (CUMS) mouse model. METHOD: The study obtained GSE84183 from th
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33552119", "kind": "science-record", "revision": 7, "content_hash": "sha256:c5bfad758427c6f2232f11a30652eb1c292188ec9ee12fedba244540f4a20bb7", "created_at": "2026-11-01T15:41:24Z", "updated_at": "2026-11-01T22:03:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression.", "doi": "10.3389/fgene.2020.589370", "pmid": "33552119", "authors": ["Jing Yang", "Chaoqin Chen", "Xiaoyuan Jin", "Lu Liu", "Jiajia Lin", "Xianhui Kang", "Shengmei Zhu"], "journal": "Frontiers in genetics", "year": 2020, "abstract": "BACKGROUND: Depression is a prevalent mental disorder, which is difficult to diagnose and treat due to its unclear pathogenic mechanisms. The discovery of novel and effective therapeutic targets for depression is urgently needed. The hippocampus is a crucial region involved in depression and has been a therapeutic target for many antidepressants. Thus, it is beneficial for comprehensive research to be carried out on the molecular mechanisms of the hippocampus involved in the pathogenesis of depression. This study aims to investigate the differentially expressed genes (DEG) in the hippocampus in a chronic unpredictable mild stress (CUMS) mouse model.\nMETHOD: The study obtained GSE84183 from the GEO database. The R language screened the differential expression genes (DEG) in the hippocampus tissue of depressed mice, and the enrichment pathways of DEGs were analyzed. A protein-protein interaction (PPI) network was constructed in the STRING database and visualized in Cytoscape software. MicroRNAs for these DEGs were obtained from TarBase and mortar base databases, and transcription factors (TF) related to DEG were predicted from the ENCODE database. Both networks used the visual analysis platform NetworkAnalyst. Finally, the microRNA-TF network was integrated based on the above two networks and imported into Cytoscape for further analysis.\nRESULTS: This study screened 325 differentially expressed genes, containing 42 downregulated genes and 283 upregulated genes. Most of these genes are enriched in the cell cycle and the chemokine signaling pathway. Meanwhile, Wfs1, one of the top ten DEGs, was identified as the key regulator of the cell cycle and the participator in the highest number of modules screened out in PPI networks. Wfs1-related molecules, including UBTF, mmu-mir-17-5p, and mmu-mir-7b-5p, were therefore screened out. Furthermore, we confirmed the downregulation of Wfs1 and upregulation of UBTF/mmu-mir-17-5p/mmu-mir-7b-5p in the hippocampus of the CUMS mouse model. Our data indicate that Wfs1 and related molecules were predicted to be associated with the pathological process of depression. 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