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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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.
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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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