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Expression of circ-PHC3 enhances ovarian cancer progression via regulation of the miR-497-5p/SOX9 pathway

BACKGROUND: Accumulating studies have reported indispensable functions of circular RNAs (circRNA) in tumor progression through regulation of gene expression. However, circRNA expression profiles and functions in human ovarian carcinoma (OC) are yet to be fully established. METHODS: In this research,...

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Autores principales: Wang, Hongxia, Lan, Suwei, Wang, Lingxiang, Zhao, Jingyun, Jia, Xinzhuan, Xu, Jie, Sun, Guangyu, Liu, Leilei, Gong, Shan, Wang, Na, Shan, Baoen, Zhang, Fenghua, Zhang, Zhengmao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357880/
https://www.ncbi.nlm.nih.gov/pubmed/37468993
http://dx.doi.org/10.1186/s13048-023-01170-w
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author Wang, Hongxia
Lan, Suwei
Wang, Lingxiang
Zhao, Jingyun
Jia, Xinzhuan
Xu, Jie
Sun, Guangyu
Liu, Leilei
Gong, Shan
Wang, Na
Shan, Baoen
Zhang, Fenghua
Zhang, Zhengmao
author_facet Wang, Hongxia
Lan, Suwei
Wang, Lingxiang
Zhao, Jingyun
Jia, Xinzhuan
Xu, Jie
Sun, Guangyu
Liu, Leilei
Gong, Shan
Wang, Na
Shan, Baoen
Zhang, Fenghua
Zhang, Zhengmao
author_sort Wang, Hongxia
collection PubMed
description BACKGROUND: Accumulating studies have reported indispensable functions of circular RNAs (circRNA) in tumor progression through regulation of gene expression. However, circRNA expression profiles and functions in human ovarian carcinoma (OC) are yet to be fully established. METHODS: In this research, deep sequencing of circRNAs from OC samples and paired adjacent normal tissues was performed to establish expression profiles and circ-PHC3 levels between the groups further compared using RT-qPCR. The effects of ectopic overexpression of miR-497-5p and SOX9 and siRNA-mediated knockdown of circ-PHC3 and an miR-497-5p inhibitor were explored to clarify the regulatory mechanisms underlying circ-PHC3 activity in OC proliferation and metastasis. Information from public databases and the luciferase reporter assay were further utilized to examine the potential correlations among circ-PHC3, miR-497-5p and SOX9. RESULTS: Our results showed significant upregulation of circ-PHC3 in both OC cell lines and tissues. In the luciferase reporter assay, downregulation of circ-PHC3 led to suppression of metastasis and proliferation, potentially through targeted effects on the miR-497-5p/SOX9 axis in OC. SOX9 overexpression or miR-497-5p suppression rescued OC cell proliferation and invasion following silencing of circ-PHC3. Moreover, SOX9 inhibition induced restoration of OC cell invasion and proliferation under conditions of overexpression of miR-497-5p. Thus, circ-PHC3 appears to exert effects on cancer stem cell differentiation through regulation of the miR-497-5p/SOX9 axis. CONCLUSION: Taken together, our findings suggest that circ-PHC3 enhances OC progression through functioning as an miR-497-5p sponge to promote SOX9 expression, supporting its potential as a promising candidate target for OC therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01170-w.
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spelling pubmed-103578802023-07-21 Expression of circ-PHC3 enhances ovarian cancer progression via regulation of the miR-497-5p/SOX9 pathway Wang, Hongxia Lan, Suwei Wang, Lingxiang Zhao, Jingyun Jia, Xinzhuan Xu, Jie Sun, Guangyu Liu, Leilei Gong, Shan Wang, Na Shan, Baoen Zhang, Fenghua Zhang, Zhengmao J Ovarian Res Research BACKGROUND: Accumulating studies have reported indispensable functions of circular RNAs (circRNA) in tumor progression through regulation of gene expression. However, circRNA expression profiles and functions in human ovarian carcinoma (OC) are yet to be fully established. METHODS: In this research, deep sequencing of circRNAs from OC samples and paired adjacent normal tissues was performed to establish expression profiles and circ-PHC3 levels between the groups further compared using RT-qPCR. The effects of ectopic overexpression of miR-497-5p and SOX9 and siRNA-mediated knockdown of circ-PHC3 and an miR-497-5p inhibitor were explored to clarify the regulatory mechanisms underlying circ-PHC3 activity in OC proliferation and metastasis. Information from public databases and the luciferase reporter assay were further utilized to examine the potential correlations among circ-PHC3, miR-497-5p and SOX9. RESULTS: Our results showed significant upregulation of circ-PHC3 in both OC cell lines and tissues. In the luciferase reporter assay, downregulation of circ-PHC3 led to suppression of metastasis and proliferation, potentially through targeted effects on the miR-497-5p/SOX9 axis in OC. SOX9 overexpression or miR-497-5p suppression rescued OC cell proliferation and invasion following silencing of circ-PHC3. Moreover, SOX9 inhibition induced restoration of OC cell invasion and proliferation under conditions of overexpression of miR-497-5p. Thus, circ-PHC3 appears to exert effects on cancer stem cell differentiation through regulation of the miR-497-5p/SOX9 axis. CONCLUSION: Taken together, our findings suggest that circ-PHC3 enhances OC progression through functioning as an miR-497-5p sponge to promote SOX9 expression, supporting its potential as a promising candidate target for OC therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01170-w. BioMed Central 2023-07-20 /pmc/articles/PMC10357880/ /pubmed/37468993 http://dx.doi.org/10.1186/s13048-023-01170-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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
Wang, Hongxia
Lan, Suwei
Wang, Lingxiang
Zhao, Jingyun
Jia, Xinzhuan
Xu, Jie
Sun, Guangyu
Liu, Leilei
Gong, Shan
Wang, Na
Shan, Baoen
Zhang, Fenghua
Zhang, Zhengmao
Expression of circ-PHC3 enhances ovarian cancer progression via regulation of the miR-497-5p/SOX9 pathway
title Expression of circ-PHC3 enhances ovarian cancer progression via regulation of the miR-497-5p/SOX9 pathway
title_full Expression of circ-PHC3 enhances ovarian cancer progression via regulation of the miR-497-5p/SOX9 pathway
title_fullStr Expression of circ-PHC3 enhances ovarian cancer progression via regulation of the miR-497-5p/SOX9 pathway
title_full_unstemmed Expression of circ-PHC3 enhances ovarian cancer progression via regulation of the miR-497-5p/SOX9 pathway
title_short Expression of circ-PHC3 enhances ovarian cancer progression via regulation of the miR-497-5p/SOX9 pathway
title_sort expression of circ-phc3 enhances ovarian cancer progression via regulation of the mir-497-5p/sox9 pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357880/
https://www.ncbi.nlm.nih.gov/pubmed/37468993
http://dx.doi.org/10.1186/s13048-023-01170-w
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