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EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression

BACKGROUND: Circular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervi...

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Autores principales: Yang, Meiqin, Hu, Haoran, Wu, Sufang, Ding, Jianyi, Yin, Bo, Huang, Baoyou, Li, Fang, Guo, Xiaoqing, Han, Lingfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069757/
https://www.ncbi.nlm.nih.gov/pubmed/35513835
http://dx.doi.org/10.1186/s13046-022-02368-4
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author Yang, Meiqin
Hu, Haoran
Wu, Sufang
Ding, Jianyi
Yin, Bo
Huang, Baoyou
Li, Fang
Guo, Xiaoqing
Han, Lingfei
author_facet Yang, Meiqin
Hu, Haoran
Wu, Sufang
Ding, Jianyi
Yin, Bo
Huang, Baoyou
Li, Fang
Guo, Xiaoqing
Han, Lingfei
author_sort Yang, Meiqin
collection PubMed
description BACKGROUND: Circular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervical cancer are still unclear.   METHODS: CircRNAs related to cervical cancer were screened through the Gene Expression Omnibus (GEO) database. qRT-PCR was used to verify the expression of circ_0087429 in cervical cancer tissues and cells. Then, in vivo and in vitro experiments were conducted to evaluate the role of circ_0087429 in the progression of cervical cancer. The role of the circ_0087429/miR-5003-3p/osteoglycin (OGN) axis in the epithelial to mesenchymal transition (EMT) was confirmed by rescue experiments, fluorescence in situ hybridization, luciferase reporter assays, immunofluorescence staining and western blotting. The inhibitory effect of Eukaryotic initiation factor 4A-III (EIF4A3) on the biogenesis of circ_0087429 was verified by RNA immunoprecipitation (RIP) assays and qRT-PCR. RESULTS: circ_0087429 is significantly downregulated in cervical cancer tissues and cells and negatively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging and lymphatic metastasis in cervical cancer patients. circ_0087429 can significantly inhibit the proliferation, migration, invasion and angiogenesis of cervical cancer in vitro and tumour growth and metastasis in vivo. OGN is significantly downregulated in cervical cancer tissues and cells. circ_0087429 can upregulate the expression of OGN by competitively binding with miR-5003-3p, thereby reversing EMT and inhibiting the progression of cervical cancer. EIF4A3 can inhibit circ_0087429 expression by binding to its flanking regions. CONCLUSIONS: As a tumour suppressor, circ_0087429 regulated by EIF4A3 can reverse EMT and inhibit the progression of cervical cancer through the miR-5003-3p/OGN axis. It is expected to become a potential target for the treatment of cervical cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-022-02368-4.
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spelling pubmed-90697572022-05-05 EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression Yang, Meiqin Hu, Haoran Wu, Sufang Ding, Jianyi Yin, Bo Huang, Baoyou Li, Fang Guo, Xiaoqing Han, Lingfei J Exp Clin Cancer Res Research BACKGROUND: Circular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervical cancer are still unclear.   METHODS: CircRNAs related to cervical cancer were screened through the Gene Expression Omnibus (GEO) database. qRT-PCR was used to verify the expression of circ_0087429 in cervical cancer tissues and cells. Then, in vivo and in vitro experiments were conducted to evaluate the role of circ_0087429 in the progression of cervical cancer. The role of the circ_0087429/miR-5003-3p/osteoglycin (OGN) axis in the epithelial to mesenchymal transition (EMT) was confirmed by rescue experiments, fluorescence in situ hybridization, luciferase reporter assays, immunofluorescence staining and western blotting. The inhibitory effect of Eukaryotic initiation factor 4A-III (EIF4A3) on the biogenesis of circ_0087429 was verified by RNA immunoprecipitation (RIP) assays and qRT-PCR. RESULTS: circ_0087429 is significantly downregulated in cervical cancer tissues and cells and negatively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging and lymphatic metastasis in cervical cancer patients. circ_0087429 can significantly inhibit the proliferation, migration, invasion and angiogenesis of cervical cancer in vitro and tumour growth and metastasis in vivo. OGN is significantly downregulated in cervical cancer tissues and cells. circ_0087429 can upregulate the expression of OGN by competitively binding with miR-5003-3p, thereby reversing EMT and inhibiting the progression of cervical cancer. EIF4A3 can inhibit circ_0087429 expression by binding to its flanking regions. CONCLUSIONS: As a tumour suppressor, circ_0087429 regulated by EIF4A3 can reverse EMT and inhibit the progression of cervical cancer through the miR-5003-3p/OGN axis. It is expected to become a potential target for the treatment of cervical cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-022-02368-4. BioMed Central 2022-05-05 /pmc/articles/PMC9069757/ /pubmed/35513835 http://dx.doi.org/10.1186/s13046-022-02368-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Meiqin
Hu, Haoran
Wu, Sufang
Ding, Jianyi
Yin, Bo
Huang, Baoyou
Li, Fang
Guo, Xiaoqing
Han, Lingfei
EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression
title EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression
title_full EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression
title_fullStr EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression
title_full_unstemmed EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression
title_short EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression
title_sort eif4a3-regulated circ_0087429 can reverse emt and inhibit the progression of cervical cancer via mir-5003-3p-dependent upregulation of ogn expression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069757/
https://www.ncbi.nlm.nih.gov/pubmed/35513835
http://dx.doi.org/10.1186/s13046-022-02368-4
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