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Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism
Myc is a well-known proto-oncogene that is frequently amplified and activated in breast cancer, especially in triple-negative breast cancer (TNBC). However, the role of circular RNA (circRNA) generated by Myc remains unclear. Herein, we found that circMyc (hsa_circ_0085533) was remarkably upregulate...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182216/ https://www.ncbi.nlm.nih.gov/pubmed/37173608 http://dx.doi.org/10.1007/s12672-023-00679-2 |
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author | Wang, Shengting Wang, Yufang Wang, Yue Li, Qian Zeng, Kaixuan Li, Xiaoming Feng, Xinghua |
author_facet | Wang, Shengting Wang, Yufang Wang, Yue Li, Qian Zeng, Kaixuan Li, Xiaoming Feng, Xinghua |
author_sort | Wang, Shengting |
collection | PubMed |
description | Myc is a well-known proto-oncogene that is frequently amplified and activated in breast cancer, especially in triple-negative breast cancer (TNBC). However, the role of circular RNA (circRNA) generated by Myc remains unclear. Herein, we found that circMyc (hsa_circ_0085533) was remarkably upregulated in TNBC tissues and cell lines, which was attributed to gene amplification. Genetic knockdown of circMyc mediated by lentiviral vector significantly inhibited TNBC cell proliferation and invasion. Importantly, circMyc increased cellular triglycerides, cholesterols and lipid droplet contents. CircMyc was detected in both cytoplasm and nucleus, cytoplasmic circMyc could directly bind to HuR protein, facilitating the binding of HuR to SREBP1 mRNA, resulting in increasing SREBP1 mRNA stability. Nuclear circMyc bound to Myc protein, facilitating the occupation of Myc on SREBP1 promoter, leading to increasing SREBP1 transcription. As a result, the elevated SREBP1 increased the expression of its downstream lipogenic enzymes, enhancing lipogenesis and TNBC progression. Moreover, the orthotopic xenograft model showed that depletion of circMyc markedly inhibited lipogenesis and reduced tumor size. Clinically, high circMyc was closely related to larger tumor volume, later clinical stage and lymph node metastasis, functioning as an adverse prognostic factor. Collectively, our findings characterize a novel Myc-derived circRNA controlling TNBC tumorigenesis via regulation of metabolic reprogramming, implying a promising therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-023-00679-2. |
format | Online Article Text |
id | pubmed-10182216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-101822162023-05-14 Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism Wang, Shengting Wang, Yufang Wang, Yue Li, Qian Zeng, Kaixuan Li, Xiaoming Feng, Xinghua Discov Oncol Research Myc is a well-known proto-oncogene that is frequently amplified and activated in breast cancer, especially in triple-negative breast cancer (TNBC). However, the role of circular RNA (circRNA) generated by Myc remains unclear. Herein, we found that circMyc (hsa_circ_0085533) was remarkably upregulated in TNBC tissues and cell lines, which was attributed to gene amplification. Genetic knockdown of circMyc mediated by lentiviral vector significantly inhibited TNBC cell proliferation and invasion. Importantly, circMyc increased cellular triglycerides, cholesterols and lipid droplet contents. CircMyc was detected in both cytoplasm and nucleus, cytoplasmic circMyc could directly bind to HuR protein, facilitating the binding of HuR to SREBP1 mRNA, resulting in increasing SREBP1 mRNA stability. Nuclear circMyc bound to Myc protein, facilitating the occupation of Myc on SREBP1 promoter, leading to increasing SREBP1 transcription. As a result, the elevated SREBP1 increased the expression of its downstream lipogenic enzymes, enhancing lipogenesis and TNBC progression. Moreover, the orthotopic xenograft model showed that depletion of circMyc markedly inhibited lipogenesis and reduced tumor size. Clinically, high circMyc was closely related to larger tumor volume, later clinical stage and lymph node metastasis, functioning as an adverse prognostic factor. Collectively, our findings characterize a novel Myc-derived circRNA controlling TNBC tumorigenesis via regulation of metabolic reprogramming, implying a promising therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-023-00679-2. Springer US 2023-05-12 /pmc/articles/PMC10182216/ /pubmed/37173608 http://dx.doi.org/10.1007/s12672-023-00679-2 Text en © The Author(s) 2023 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/) . |
spellingShingle | Research Wang, Shengting Wang, Yufang Wang, Yue Li, Qian Zeng, Kaixuan Li, Xiaoming Feng, Xinghua Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism |
title | Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism |
title_full | Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism |
title_fullStr | Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism |
title_full_unstemmed | Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism |
title_short | Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism |
title_sort | myc derived circrna promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182216/ https://www.ncbi.nlm.nih.gov/pubmed/37173608 http://dx.doi.org/10.1007/s12672-023-00679-2 |
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