Cargando…

CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1

BACKGROUND: Cytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet. METHODS: The expression of CTPS1 in TNBC tissues was deter...

Descripción completa

Detalles Bibliográficos
Autores principales: Lin, Yuxiang, Zhang, Jie, Li, Yan, Guo, Wenhui, Chen, Lili, Chen, Minyan, Chen, Xiaobin, Zhang, Wenzhe, Jin, Xuan, Jiang, Meichen, Xiao, Han, Wang, Chuan, Song, Chuangui, Fu, Fangmeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8734240/
https://www.ncbi.nlm.nih.gov/pubmed/34991621
http://dx.doi.org/10.1186/s12967-021-03206-5
_version_ 1784627974923878400
author Lin, Yuxiang
Zhang, Jie
Li, Yan
Guo, Wenhui
Chen, Lili
Chen, Minyan
Chen, Xiaobin
Zhang, Wenzhe
Jin, Xuan
Jiang, Meichen
Xiao, Han
Wang, Chuan
Song, Chuangui
Fu, Fangmeng
author_facet Lin, Yuxiang
Zhang, Jie
Li, Yan
Guo, Wenhui
Chen, Lili
Chen, Minyan
Chen, Xiaobin
Zhang, Wenzhe
Jin, Xuan
Jiang, Meichen
Xiao, Han
Wang, Chuan
Song, Chuangui
Fu, Fangmeng
author_sort Lin, Yuxiang
collection PubMed
description BACKGROUND: Cytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet. METHODS: The expression of CTPS1 in TNBC tissues was determined by GEO, TCGA databases and immunohistochemistry (IHC). The effect of CTPS1 on TNBC cell proliferation, migration, invasion, apoptosis and tumorigenesis were explored in vivo and in vitro. In addition, the transcription factor Y-box binding protein 1 (YBX1) was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. Pearson correlation analysis was utilized to assess the association between YBX1 and CTPS1 expression. RESULTS: CTPS1 expression was significantly upregulated in TNBC tissues and cell lines. Higher CTPS1 expression was correlated with a poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Silencing of CTPS1 dramatically inhibited the proliferation, migration, invasion ability and induced apoptosis of MDA-MB-231 and HCC1937 cells. Xenograft tumor model also indicated that CTPS1 knockdown remarkably reduced tumor growth in mice. Mechanically, YBX1 could bind to the promoter of CTPS1 to promote its transcription. Furthermore, the expression of YBX1 was positively correlated with CTPS1 in TNBC tissues. Rescue experiments confirmed that the enhanced cell proliferation and invasion ability induced by YBX1 overexpression could be reversed by CTPS1 knockdown. CONCLUSION: Our data demonstrate that YBX1/CTPS1 axis plays an important role in the progression of TNBC. CTPS1 might be a promising prognosis biomarker and potential therapeutic target for patients with triple-negative breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03206-5.
format Online
Article
Text
id pubmed-8734240
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-87342402022-01-07 CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1 Lin, Yuxiang Zhang, Jie Li, Yan Guo, Wenhui Chen, Lili Chen, Minyan Chen, Xiaobin Zhang, Wenzhe Jin, Xuan Jiang, Meichen Xiao, Han Wang, Chuan Song, Chuangui Fu, Fangmeng J Transl Med Research BACKGROUND: Cytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet. METHODS: The expression of CTPS1 in TNBC tissues was determined by GEO, TCGA databases and immunohistochemistry (IHC). The effect of CTPS1 on TNBC cell proliferation, migration, invasion, apoptosis and tumorigenesis were explored in vivo and in vitro. In addition, the transcription factor Y-box binding protein 1 (YBX1) was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. Pearson correlation analysis was utilized to assess the association between YBX1 and CTPS1 expression. RESULTS: CTPS1 expression was significantly upregulated in TNBC tissues and cell lines. Higher CTPS1 expression was correlated with a poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Silencing of CTPS1 dramatically inhibited the proliferation, migration, invasion ability and induced apoptosis of MDA-MB-231 and HCC1937 cells. Xenograft tumor model also indicated that CTPS1 knockdown remarkably reduced tumor growth in mice. Mechanically, YBX1 could bind to the promoter of CTPS1 to promote its transcription. Furthermore, the expression of YBX1 was positively correlated with CTPS1 in TNBC tissues. Rescue experiments confirmed that the enhanced cell proliferation and invasion ability induced by YBX1 overexpression could be reversed by CTPS1 knockdown. CONCLUSION: Our data demonstrate that YBX1/CTPS1 axis plays an important role in the progression of TNBC. CTPS1 might be a promising prognosis biomarker and potential therapeutic target for patients with triple-negative breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03206-5. BioMed Central 2022-01-06 /pmc/articles/PMC8734240/ /pubmed/34991621 http://dx.doi.org/10.1186/s12967-021-03206-5 Text en © The Author(s) 2022 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/) . 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
Lin, Yuxiang
Zhang, Jie
Li, Yan
Guo, Wenhui
Chen, Lili
Chen, Minyan
Chen, Xiaobin
Zhang, Wenzhe
Jin, Xuan
Jiang, Meichen
Xiao, Han
Wang, Chuan
Song, Chuangui
Fu, Fangmeng
CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1
title CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1
title_full CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1
title_fullStr CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1
title_full_unstemmed CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1
title_short CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1
title_sort ctps1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by ybx1
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8734240/
https://www.ncbi.nlm.nih.gov/pubmed/34991621
http://dx.doi.org/10.1186/s12967-021-03206-5
work_keys_str_mv AT linyuxiang ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT zhangjie ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT liyan ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT guowenhui ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT chenlili ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT chenminyan ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT chenxiaobin ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT zhangwenzhe ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT jinxuan ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT jiangmeichen ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT xiaohan ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT wangchuan ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT songchuangui ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1
AT fufangmeng ctps1promotesmalignantprogressionoftriplenegativebreastcancerwithtranscriptionalactivationbyybx1