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Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis

BACKGROUND: There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 ex...

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Autores principales: Gao, Zhihui, Wang, Qianqing, Ji, Mei, Guo, Xiangcui, Li, Li, Su, Xiaoke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165805/
https://www.ncbi.nlm.nih.gov/pubmed/34053467
http://dx.doi.org/10.1186/s12967-021-02872-9
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author Gao, Zhihui
Wang, Qianqing
Ji, Mei
Guo, Xiangcui
Li, Li
Su, Xiaoke
author_facet Gao, Zhihui
Wang, Qianqing
Ji, Mei
Guo, Xiangcui
Li, Li
Su, Xiaoke
author_sort Gao, Zhihui
collection PubMed
description BACKGROUND: There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 expression. METHODS: CC stem cells (CD133(+)CaSki) and exosomes were extracted and identified. The synthesized UCA1- and miR-122-5p-related sequences were transfected into CaSki cells, CaSki cells-derived exosomes were extracted and then co-cultured with CD133(+)CaSki cells. The functional roles of UCA1 and miR-122-5p in self-renewal and differentiation ability of CC stem cells were determined using ectopic expression, knockdown/depletion and reporter assay experiments. An in vivo experiment was performed to verify the in vitro results. RESULTS: Up-regulated UCA1 and SOX2 and down-regulated miR-122-5p were found in CaSki-Exo. Exosomes promoted invasion, migration, proliferation and restrained apoptosis of CD133(+)CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133(+)CaSki cells while advanced apoptosis and suppressed the tumor volume and weight in nude mice. CONCLUSION: Our study provides evidence that CaSki-Exo can promote the self-renewal and differentiation ability of CC stem cells while silencing UCA1 or up-regulating miR-122-5p restrains self-renewal and differentiation of CC stem cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02872-9.
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spelling pubmed-81658052021-06-01 Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis Gao, Zhihui Wang, Qianqing Ji, Mei Guo, Xiangcui Li, Li Su, Xiaoke J Transl Med Research BACKGROUND: There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 expression. METHODS: CC stem cells (CD133(+)CaSki) and exosomes were extracted and identified. The synthesized UCA1- and miR-122-5p-related sequences were transfected into CaSki cells, CaSki cells-derived exosomes were extracted and then co-cultured with CD133(+)CaSki cells. The functional roles of UCA1 and miR-122-5p in self-renewal and differentiation ability of CC stem cells were determined using ectopic expression, knockdown/depletion and reporter assay experiments. An in vivo experiment was performed to verify the in vitro results. RESULTS: Up-regulated UCA1 and SOX2 and down-regulated miR-122-5p were found in CaSki-Exo. Exosomes promoted invasion, migration, proliferation and restrained apoptosis of CD133(+)CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133(+)CaSki cells while advanced apoptosis and suppressed the tumor volume and weight in nude mice. CONCLUSION: Our study provides evidence that CaSki-Exo can promote the self-renewal and differentiation ability of CC stem cells while silencing UCA1 or up-regulating miR-122-5p restrains self-renewal and differentiation of CC stem cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02872-9. BioMed Central 2021-05-30 /pmc/articles/PMC8165805/ /pubmed/34053467 http://dx.doi.org/10.1186/s12967-021-02872-9 Text en © The Author(s) 2021 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
Gao, Zhihui
Wang, Qianqing
Ji, Mei
Guo, Xiangcui
Li, Li
Su, Xiaoke
Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis
title Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis
title_full Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis
title_fullStr Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis
title_full_unstemmed Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis
title_short Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis
title_sort exosomal lncrna uca1 modulates cervical cancer stem cell self-renewal and differentiation through microrna-122-5p/sox2 axis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165805/
https://www.ncbi.nlm.nih.gov/pubmed/34053467
http://dx.doi.org/10.1186/s12967-021-02872-9
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