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Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway

BACKGROUND: The purpose of this study was to investigate the role of hsa_circRNA_102051 in colorectal cancer (CRC) and its effect on the stemness of tumor cells. METHODS: CircRNA microarray was under analysis to screen differentially expressed novel circRNAs in the pathology of CRC. Quantitative rea...

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Autores principales: Chen, Zhongsheng, Cheng, Haiyu, Zhang, Jiandong, Jiang, Dongbing, Chen, Gang, Yan, Shunkang, Chen, Wen, Zhan, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552285/
https://www.ncbi.nlm.nih.gov/pubmed/37794386
http://dx.doi.org/10.1186/s12935-023-03026-1
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author Chen, Zhongsheng
Cheng, Haiyu
Zhang, Jiandong
Jiang, Dongbing
Chen, Gang
Yan, Shunkang
Chen, Wen
Zhan, Wei
author_facet Chen, Zhongsheng
Cheng, Haiyu
Zhang, Jiandong
Jiang, Dongbing
Chen, Gang
Yan, Shunkang
Chen, Wen
Zhan, Wei
author_sort Chen, Zhongsheng
collection PubMed
description BACKGROUND: The purpose of this study was to investigate the role of hsa_circRNA_102051 in colorectal cancer (CRC) and its effect on the stemness of tumor cells. METHODS: CircRNA microarray was under analysis to screen differentially expressed novel circRNAs in the pathology of CRC. Quantitative real-time PCR was used to detect the relative RNA expression in CRC cells and samples. The effects of hsa_circRNA_102051 on biological functions in CRC cells were accessed both in vitro and in vivo. FISH, RIP and luciferase reporter assay were conducted to confirm the regulatory correlations between hsa_circRNA_102051 and miR-203a, as well as miR-203a and BPTF. Xenograft models were applied to further verify the impacts and fluctuations of hsa_circRNA_102051/miR-203a/BPTF. Moreover, the mechanism how hsa_circRNA_102051 affected the Notch signals was also elucidated. RESULTS: Hsa_circRNA_102051 was up-regulated in CRC tissues and cell lines, capable to promote the growth and invasion of CRC. In addition, hsa_circRNA_102051 could enhance stemness of CRC cells. BPTF was identified as downstream factors of hsa_circRNA_102051, and miR-203a was determined directly targeting both hsa_circRNA_102051 and BPTF as an intermediate regulator. Hsa_circRNA_102051 in CRC could block miR-203a expression, and subsequently activated BPTF. Hsa_circRNA_102051/miR-203a/BPTF axis modulated stemness of CRC cells by affecting Notch pathway. CONCLUSIONS: Our findings provided new clues that hsa_circRNA_102051 might be a potential predictive or prognostic factor in CRC, which induced the fluctuation of downstream miR-203a/BPTF, and subsequently influenced tumor growth, activities and stemness. Thereinto, the Notch signals were also involved. Hence, the hsa_circRNA_102051/miR-203a/BPTF axis could be further explored as a therapeutic target for anti-metastatic therapy in CRC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03026-1.
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spelling pubmed-105522852023-10-06 Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway Chen, Zhongsheng Cheng, Haiyu Zhang, Jiandong Jiang, Dongbing Chen, Gang Yan, Shunkang Chen, Wen Zhan, Wei Cancer Cell Int Research BACKGROUND: The purpose of this study was to investigate the role of hsa_circRNA_102051 in colorectal cancer (CRC) and its effect on the stemness of tumor cells. METHODS: CircRNA microarray was under analysis to screen differentially expressed novel circRNAs in the pathology of CRC. Quantitative real-time PCR was used to detect the relative RNA expression in CRC cells and samples. The effects of hsa_circRNA_102051 on biological functions in CRC cells were accessed both in vitro and in vivo. FISH, RIP and luciferase reporter assay were conducted to confirm the regulatory correlations between hsa_circRNA_102051 and miR-203a, as well as miR-203a and BPTF. Xenograft models were applied to further verify the impacts and fluctuations of hsa_circRNA_102051/miR-203a/BPTF. Moreover, the mechanism how hsa_circRNA_102051 affected the Notch signals was also elucidated. RESULTS: Hsa_circRNA_102051 was up-regulated in CRC tissues and cell lines, capable to promote the growth and invasion of CRC. In addition, hsa_circRNA_102051 could enhance stemness of CRC cells. BPTF was identified as downstream factors of hsa_circRNA_102051, and miR-203a was determined directly targeting both hsa_circRNA_102051 and BPTF as an intermediate regulator. Hsa_circRNA_102051 in CRC could block miR-203a expression, and subsequently activated BPTF. Hsa_circRNA_102051/miR-203a/BPTF axis modulated stemness of CRC cells by affecting Notch pathway. CONCLUSIONS: Our findings provided new clues that hsa_circRNA_102051 might be a potential predictive or prognostic factor in CRC, which induced the fluctuation of downstream miR-203a/BPTF, and subsequently influenced tumor growth, activities and stemness. Thereinto, the Notch signals were also involved. Hence, the hsa_circRNA_102051/miR-203a/BPTF axis could be further explored as a therapeutic target for anti-metastatic therapy in CRC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03026-1. BioMed Central 2023-10-05 /pmc/articles/PMC10552285/ /pubmed/37794386 http://dx.doi.org/10.1186/s12935-023-03026-1 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
Chen, Zhongsheng
Cheng, Haiyu
Zhang, Jiandong
Jiang, Dongbing
Chen, Gang
Yan, Shunkang
Chen, Wen
Zhan, Wei
Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway
title Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway
title_full Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway
title_fullStr Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway
title_full_unstemmed Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway
title_short Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway
title_sort hsa_circrna_102051 regulates colorectal cancer proliferation and metastasis by mediating notch pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552285/
https://www.ncbi.nlm.nih.gov/pubmed/37794386
http://dx.doi.org/10.1186/s12935-023-03026-1
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