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Title:
RETRACTED ARTICLE: The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer | Cellular Oncology
Description:
Purpose Growing evidence indicates that aberrant expression of microRNAs contributes to tumor development. However, the biological role of microRNA-4490 (miR-4490) in gastric cancer (GC) remains to be clarified. Methods To explore the function of miR-4490 in GC, we performed colony formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization (ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase reporter assays. In addition, the growth, migration and invasion capacities of GC cells were evaluated. Results We found that miR-4490 was significantly downregulated in primary GC samples and in GC-derived cell lines compared with normal controls, and that this expression level was negatively correlated with GC malignancy. Exogenous miR-4490 expression not only reduced cell cycle progression and proliferation, but also significantly inhibited GC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that miR-4490 directly targets USP22, which mediates inhibition of GC cell proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we found through luciferase and ChIP assays that transcription factor POU2F1 can directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters and, by doing so, modulate their transcription. Spearmanās correlation analysis revealed a positive correlation between USP22 and POU2F1 expression and negative correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1 expression in primary GC tissues. Conclusion Based on our results we conclude that miR-4490 acts as a tumor suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in the regulation of growth, invasion and EMT of GC cells.
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Keywords {š}
cells, expression, usp, fig, pouf, cell, cancer, article, found, invasion, google, scholar, liu, metastasis, tissues, compared, proliferation, wang, emt, gastric, group, vector, decreased, zhang, promoter, mnc, levels, ecadherin, analysis, data, chen, migration, progression, china, transfected, mice, performed, assays, growth, usa, increased, human, supplementary, yang, tumor, assay, utr, vimentin, luciferase, results,
Topics {āļø}
activating c-myc/nampt/sirt1-dependent foxo1 ubi-mcs-sv40- egfp-ires es/cgi-bin/promo_v3/promo/promoinit erbb4/pik3r3/mtor/s6k2 signaling pathway alkaline phosphatase-conjugated anti-digoxigenin pou2f1-mir-4490-usp22 signaling axis pou2f1/mir-4490/usp22 signaling axis pou2f1/mir-4490/usp22 axis plays i-nc-transfected cells displayed synbindin-related erk signalling mir-4490/pou2f1-overexpressing group exhibited intimate cell-cell contacts activates wnt/pcp pathway c-jun promotes proliferation semi-quantitative scoring system akt-pou2f1-ecd signalling puromycin-resistant cell pools induces epithelial-mesenchymal transition mir-584-5p inhibits proliferation mouse anti-cyclin b1 dna polymerase-primase complex specific pathogen-free conditions pou2f1/mir-4490/usp22 axis dig-labeled mir-4490 probe gc-derived cell lines quantitative real-time pcr small-cell lung cancer inhibit foxk1-mediated proliferation dual-luciferase reporter assay epithelial marker e-cadherin gc cell cycle progression promotes cell growth pou2f1/mir-4490 group exhibited microrna-193a-3p pou2f1-mediated gc development normal gastric mucosa de/apps/zmf/mirwalk2/ dual-luciferase reporter assays human gastric cancer article download pdf inverted phase-contrast microscope pou2f1-mir-4490 interaction tests pou2f1-expressing cells decreased significant g1/g0 arrest mir-4490-mediated usp22 downregulation pou2f1-overexpressing gc cells human epithelial cancer mir-4490-overexpressing gc cells γ-catenin expression levels vector/mimic-nc group
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mainEntity:
headline:RETRACTED ARTICLE: The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer
description:Growing evidence indicates that aberrant expression of microRNAs
contributes to tumor development. However, the biological role of microRNA-4490
(miR-4490) in gastric cancer (GC) remains to be clarified. To explore the function of miR-4490 in GC, we performed colony
formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization
(ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase
reporter assays. In addition, the growth, migration and invasion capacities of
GC cells were evaluated. We found that miR-4490 was significantly downregulated in primary GC
samples and in GC-derived cell lines compared with normal controls, and that
this expression level was negatively correlated with GC malignancy. Exogenous
miR-4490 expression not only reduced cell cycle progression and proliferation,
but also significantly inhibited GC cell migration, invasion and
epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that
miR-4490 directly targets USP22, which mediates inhibition of GC cell
proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we
found through luciferase and ChIP assays that transcription factor POU2F1 can
directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters
and, by doing so, modulate their transcription. Spearmanās correlation analysis
revealed a positive correlation between USP22 and POU2F1 expression and negative
correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1
expression in primary GC tissues. Based on our results we conclude that miR-4490 acts as a tumor
suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in
the regulation of growth, invasion and EMT of GC cells.
datePublished:2020-08-28T00:00:00Z
dateModified:2022-12-29T00:00:00Z
pageStart:1017
pageEnd:1033
license:http://creativecommons.org/licenses/by/4.0/
sameAs:https://doi.org/10.1007/s13402-020-00553-1
keywords:
Gastric cancer
Metastasis
MiR-4490
POU2F1
Epithelial-mesenchymal transition
Cancer Research
Biomedicine
general
Pathology
Oncology
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ScholarlyArticle:
headline:RETRACTED ARTICLE: The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer
description:Growing evidence indicates that aberrant expression of microRNAs
contributes to tumor development. However, the biological role of microRNA-4490
(miR-4490) in gastric cancer (GC) remains to be clarified. To explore the function of miR-4490 in GC, we performed colony
formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization
(ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase
reporter assays. In addition, the growth, migration and invasion capacities of
GC cells were evaluated. We found that miR-4490 was significantly downregulated in primary GC
samples and in GC-derived cell lines compared with normal controls, and that
this expression level was negatively correlated with GC malignancy. Exogenous
miR-4490 expression not only reduced cell cycle progression and proliferation,
but also significantly inhibited GC cell migration, invasion and
epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that
miR-4490 directly targets USP22, which mediates inhibition of GC cell
proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we
found through luciferase and ChIP assays that transcription factor POU2F1 can
directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters
and, by doing so, modulate their transcription. Spearmanās correlation analysis
revealed a positive correlation between USP22 and POU2F1 expression and negative
correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1
expression in primary GC tissues. Based on our results we conclude that miR-4490 acts as a tumor
suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in
the regulation of growth, invasion and EMT of GC cells.
datePublished:2020-08-28T00:00:00Z
dateModified:2022-12-29T00:00:00Z
pageStart:1017
pageEnd:1033
license:http://creativecommons.org/licenses/by/4.0/
sameAs:https://doi.org/10.1007/s13402-020-00553-1
keywords:
Gastric cancer
Metastasis
MiR-4490
POU2F1
Epithelial-mesenchymal transition
Cancer Research
Biomedicine
general
Pathology
Oncology
image:
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name:Guangdong Provincial Key Laboratory of Gastroenterology, Department of
Gastroenterology, Department of Digestive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
name:Guangdong Provincial Key Laboratory of Gastroenterology, Department of
Gastroenterology, Department of Digestive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
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name:Department of Gastroenterology, Longgang District Peopleās Hospital, Shenzhen, China
name:Department of Medical Oncology, the First peopleās Hospital of Yunnan Province, Medical School of Kunming
University of Science and Technology, Kunming, China
name:Guangdong Provincial Key Laboratory of Gastroenterology, Department of
Gastroenterology, Department of Digestive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
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University, Guangzhou, Peopleās Republic of China
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Gastroenterology, Department of Digestive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
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