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CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner

Circular RNAs (circRNAs) play vital regulatory roles in the progression of multiple cancers. In our study, transcriptome analysis and self-organizing maps (SOM) were applied to screen backbone circRNAs in gastric cancer (GC). Upon validation of the expression patterns of screened circRNAs, gain- and...

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Autores principales: Qiu, Shengkui, Li, Bowen, Xia, Yiwen, Xuan, Zhe, Li, Zheng, Xie, Li, Gu, Chao, Lv, Jialun, Lu, Chen, Jiang, Tianlu, Fang, Lang, Xu, Penghui, Yang, Jing, Li, Ying, Chen, Zetian, Zhang, Lu, Wang, Linjun, Zhang, Diancai, Xu, Hao, Wang, Weizhi, Xu, Zekuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949653/
https://www.ncbi.nlm.nih.gov/pubmed/35338119
http://dx.doi.org/10.1038/s41419-022-04720-0
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author Qiu, Shengkui
Li, Bowen
Xia, Yiwen
Xuan, Zhe
Li, Zheng
Xie, Li
Gu, Chao
Lv, Jialun
Lu, Chen
Jiang, Tianlu
Fang, Lang
Xu, Penghui
Yang, Jing
Li, Ying
Chen, Zetian
Zhang, Lu
Wang, Linjun
Zhang, Diancai
Xu, Hao
Wang, Weizhi
Xu, Zekuan
author_facet Qiu, Shengkui
Li, Bowen
Xia, Yiwen
Xuan, Zhe
Li, Zheng
Xie, Li
Gu, Chao
Lv, Jialun
Lu, Chen
Jiang, Tianlu
Fang, Lang
Xu, Penghui
Yang, Jing
Li, Ying
Chen, Zetian
Zhang, Lu
Wang, Linjun
Zhang, Diancai
Xu, Hao
Wang, Weizhi
Xu, Zekuan
author_sort Qiu, Shengkui
collection PubMed
description Circular RNAs (circRNAs) play vital regulatory roles in the progression of multiple cancers. In our study, transcriptome analysis and self-organizing maps (SOM) were applied to screen backbone circRNAs in gastric cancer (GC). Upon validation of the expression patterns of screened circRNAs, gain- and loss-of-function assays were performed in vitro and in vivo. Underlying mechanisms were investigated using RNA pull-down, luciferase reporter assay and RNA immunoprecipitation. The expression of circTHBS1 was significantly increased in GC and associated with poor prognosis. CircTHBS1 facilitated the malignant behavior and epithelial-to-mesenchymal transition of GC cells. Mechanistically, circTHBS1 sponged miR-204-5p to promote the expression of Inhibin Subunit Beta A (INHBA). Moreover, circTHBS1 could enhance the HuR-mediated mRNA stability of INHBA, which subsequently activated the TGF-β pathway. Our research identified circTHBS1 as an oncogenic circRNA that enhances GC malignancy by elevating INHBA expression, providing new insight and a feasible target for the diagnosis and treatment of GC.
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spelling pubmed-89496532022-03-25 CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner Qiu, Shengkui Li, Bowen Xia, Yiwen Xuan, Zhe Li, Zheng Xie, Li Gu, Chao Lv, Jialun Lu, Chen Jiang, Tianlu Fang, Lang Xu, Penghui Yang, Jing Li, Ying Chen, Zetian Zhang, Lu Wang, Linjun Zhang, Diancai Xu, Hao Wang, Weizhi Xu, Zekuan Cell Death Dis Article Circular RNAs (circRNAs) play vital regulatory roles in the progression of multiple cancers. In our study, transcriptome analysis and self-organizing maps (SOM) were applied to screen backbone circRNAs in gastric cancer (GC). Upon validation of the expression patterns of screened circRNAs, gain- and loss-of-function assays were performed in vitro and in vivo. Underlying mechanisms were investigated using RNA pull-down, luciferase reporter assay and RNA immunoprecipitation. The expression of circTHBS1 was significantly increased in GC and associated with poor prognosis. CircTHBS1 facilitated the malignant behavior and epithelial-to-mesenchymal transition of GC cells. Mechanistically, circTHBS1 sponged miR-204-5p to promote the expression of Inhibin Subunit Beta A (INHBA). Moreover, circTHBS1 could enhance the HuR-mediated mRNA stability of INHBA, which subsequently activated the TGF-β pathway. Our research identified circTHBS1 as an oncogenic circRNA that enhances GC malignancy by elevating INHBA expression, providing new insight and a feasible target for the diagnosis and treatment of GC. Nature Publishing Group UK 2022-03-25 /pmc/articles/PMC8949653/ /pubmed/35338119 http://dx.doi.org/10.1038/s41419-022-04720-0 Text en © The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Qiu, Shengkui
Li, Bowen
Xia, Yiwen
Xuan, Zhe
Li, Zheng
Xie, Li
Gu, Chao
Lv, Jialun
Lu, Chen
Jiang, Tianlu
Fang, Lang
Xu, Penghui
Yang, Jing
Li, Ying
Chen, Zetian
Zhang, Lu
Wang, Linjun
Zhang, Diancai
Xu, Hao
Wang, Weizhi
Xu, Zekuan
CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner
title CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner
title_full CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner
title_fullStr CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner
title_full_unstemmed CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner
title_short CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner
title_sort circthbs1 drives gastric cancer progression by increasing inhba mrna expression and stability in a cerna- and rbp-dependent manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949653/
https://www.ncbi.nlm.nih.gov/pubmed/35338119
http://dx.doi.org/10.1038/s41419-022-04720-0
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