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A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels
Tumor initiation, development, and relapse may be closely associated with cancer stem cells (CSCs). The complicated mechanisms underlying the maintenance of CSCs are keeping in illustration. Long noncoding RNAs (lncRNAs), due to their multifunction in various biological processes, have been indicate...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088435/ https://www.ncbi.nlm.nih.gov/pubmed/33934099 http://dx.doi.org/10.1038/s41419-021-03708-6 |
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author | Wen, Siyang Qin, Yilu Wang, Rui Yang, Liping Zeng, Huan Zhu, Pengpeng Li, Qiao Qiu, Yuxiang Chen, Shanchun Liu, Yongcan Hou, Yixuan Tang, Xi Liu, Manran Tu, Gang |
author_facet | Wen, Siyang Qin, Yilu Wang, Rui Yang, Liping Zeng, Huan Zhu, Pengpeng Li, Qiao Qiu, Yuxiang Chen, Shanchun Liu, Yongcan Hou, Yixuan Tang, Xi Liu, Manran Tu, Gang |
author_sort | Wen, Siyang |
collection | PubMed |
description | Tumor initiation, development, and relapse may be closely associated with cancer stem cells (CSCs). The complicated mechanisms underlying the maintenance of CSCs are keeping in illustration. Long noncoding RNAs (lncRNAs), due to their multifunction in various biological processes, have been indicated to play a crucial role in CSC renewal and stemness maintenance. Using lncRNA array, we identified a novel lncRNA (named lnc408) in epithelial–mesenchymal transition-related breast CSCs (BCSCs). The lnc408 is high expressed in BCSCs in vitro and in vivo. The enhanced lnc408 is critical to BCSC characteristics and tumorigenesis. Lnc408 can recruit transcript factor SP3 to CBY1 promoter to serve as an inhibitor in CBY1 transcription in BCSCs. The high expressed CBY1 in non-BCSC interacts with 14-3-3 and β-catenin to form a ternary complex, which leads a translocation of the ternary complex into cytoplasm from nucleus and degradation of β-catenin in phosphorylation-dependent pattern. The lnc408-mediated decrease of CBY1 in BCSCs impairs the formation of 14-3-3/β-catenin/CBY1 complex, and keeps β-catenin in nucleus to promote CSC-associated CD44, SOX2, Nanog, Klf4, and c-Myc expressions and contributes to mammosphere formation; however, restoration of CBY1 expression in tumor cells reduces BCSC and its enrichment, thus lnc408 plays an essential role in maintenance of BCSC stemness. In shortly, these findings highlight that the novel lnc408 functions as an oncogenic factor by recruiting SP3 to inhibit CBY1 expression and β-catenin accumulation in nucleus to maintain stemness properties of BCSCs. Lnc408–CBY1–β-catenin signaling axis might serve as a new diagnostic and therapeutic target for breast cancer. |
format | Online Article Text |
id | pubmed-8088435 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80884352021-05-05 A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels Wen, Siyang Qin, Yilu Wang, Rui Yang, Liping Zeng, Huan Zhu, Pengpeng Li, Qiao Qiu, Yuxiang Chen, Shanchun Liu, Yongcan Hou, Yixuan Tang, Xi Liu, Manran Tu, Gang Cell Death Dis Article Tumor initiation, development, and relapse may be closely associated with cancer stem cells (CSCs). The complicated mechanisms underlying the maintenance of CSCs are keeping in illustration. Long noncoding RNAs (lncRNAs), due to their multifunction in various biological processes, have been indicated to play a crucial role in CSC renewal and stemness maintenance. Using lncRNA array, we identified a novel lncRNA (named lnc408) in epithelial–mesenchymal transition-related breast CSCs (BCSCs). The lnc408 is high expressed in BCSCs in vitro and in vivo. The enhanced lnc408 is critical to BCSC characteristics and tumorigenesis. Lnc408 can recruit transcript factor SP3 to CBY1 promoter to serve as an inhibitor in CBY1 transcription in BCSCs. The high expressed CBY1 in non-BCSC interacts with 14-3-3 and β-catenin to form a ternary complex, which leads a translocation of the ternary complex into cytoplasm from nucleus and degradation of β-catenin in phosphorylation-dependent pattern. The lnc408-mediated decrease of CBY1 in BCSCs impairs the formation of 14-3-3/β-catenin/CBY1 complex, and keeps β-catenin in nucleus to promote CSC-associated CD44, SOX2, Nanog, Klf4, and c-Myc expressions and contributes to mammosphere formation; however, restoration of CBY1 expression in tumor cells reduces BCSC and its enrichment, thus lnc408 plays an essential role in maintenance of BCSC stemness. In shortly, these findings highlight that the novel lnc408 functions as an oncogenic factor by recruiting SP3 to inhibit CBY1 expression and β-catenin accumulation in nucleus to maintain stemness properties of BCSCs. Lnc408–CBY1–β-catenin signaling axis might serve as a new diagnostic and therapeutic target for breast cancer. Nature Publishing Group UK 2021-05-01 /pmc/articles/PMC8088435/ /pubmed/33934099 http://dx.doi.org/10.1038/s41419-021-03708-6 Text en © The Author(s) 2021 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 Wen, Siyang Qin, Yilu Wang, Rui Yang, Liping Zeng, Huan Zhu, Pengpeng Li, Qiao Qiu, Yuxiang Chen, Shanchun Liu, Yongcan Hou, Yixuan Tang, Xi Liu, Manran Tu, Gang A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels |
title | A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels |
title_full | A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels |
title_fullStr | A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels |
title_full_unstemmed | A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels |
title_short | A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels |
title_sort | novel lnc408 maintains breast cancer stem cell stemness by recruiting sp3 to suppress cby1 transcription and increasing nuclear β-catenin levels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088435/ https://www.ncbi.nlm.nih.gov/pubmed/33934099 http://dx.doi.org/10.1038/s41419-021-03708-6 |
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