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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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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. |
format | Online Article Text |
id | pubmed-8949653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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