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SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation

BACKGROUND: SNRPD1 is a spliceosome-associated protein and has previously been implicated with important roles in cancer development. METHODS: Through analyzing the differential expression patterns and clinical association of splicing associated genes among tumor and tumor adjacent samples across di...

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Autores principales: Dai, Xiaofeng, Yu, Lihui, Chen, Xiao, Zhang, Jianying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059192/
https://www.ncbi.nlm.nih.gov/pubmed/33879154
http://dx.doi.org/10.1186/s12935-021-01932-w
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author Dai, Xiaofeng
Yu, Lihui
Chen, Xiao
Zhang, Jianying
author_facet Dai, Xiaofeng
Yu, Lihui
Chen, Xiao
Zhang, Jianying
author_sort Dai, Xiaofeng
collection PubMed
description BACKGROUND: SNRPD1 is a spliceosome-associated protein and has previously been implicated with important roles in cancer development. METHODS: Through analyzing the differential expression patterns and clinical association of splicing associated genes among tumor and tumor adjacent samples across different tumors and among different breast cancer subtypes, we identify the tumor promotive role of SNRPD1 using multiple publicly available datasets. Through pathway, gene ontology enrichment analysis and network construction, we linked the onco-therapeutic role of SNRPD1 with cell cycle. Via a series of experimental studies including knockdown assay, qPCR, western blotting, cell cycle, drug response assay, we confirmed the higher expression of SNPRD1 at both gene and protein expression levels in triple negative breast cancer cells, as well as its roles in promoting cell cycle and chemotherapy response. RESULTS: Our study revealed that SNRPD1 over-expression was significantly associated with genes involved in cell cycle, cell mitosis and chromatin replication, and silencing SNRPD1 in breast cancer cells could lead to halted tumor cell growth and cell cycle arrest at the G(0)/G(1) stage. We also found that triple negative breast cancer cells with reduced SNRPD1 expression lost certain sensitivity to doxorubicin whereas luminal cancer cells did not. CONCLUSIONS: Our results suggested the prognostic value of SNRPD1 on breast cancer survival, its potential as the therapeutic target halting cell cycle progression for breast cancer control, and warranted special attention on the combined use of doxorubicin and drugs targeting SNRPD1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01932-w.
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spelling pubmed-80591922021-04-21 SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation Dai, Xiaofeng Yu, Lihui Chen, Xiao Zhang, Jianying Cancer Cell Int Primary Research BACKGROUND: SNRPD1 is a spliceosome-associated protein and has previously been implicated with important roles in cancer development. METHODS: Through analyzing the differential expression patterns and clinical association of splicing associated genes among tumor and tumor adjacent samples across different tumors and among different breast cancer subtypes, we identify the tumor promotive role of SNRPD1 using multiple publicly available datasets. Through pathway, gene ontology enrichment analysis and network construction, we linked the onco-therapeutic role of SNRPD1 with cell cycle. Via a series of experimental studies including knockdown assay, qPCR, western blotting, cell cycle, drug response assay, we confirmed the higher expression of SNPRD1 at both gene and protein expression levels in triple negative breast cancer cells, as well as its roles in promoting cell cycle and chemotherapy response. RESULTS: Our study revealed that SNRPD1 over-expression was significantly associated with genes involved in cell cycle, cell mitosis and chromatin replication, and silencing SNRPD1 in breast cancer cells could lead to halted tumor cell growth and cell cycle arrest at the G(0)/G(1) stage. We also found that triple negative breast cancer cells with reduced SNRPD1 expression lost certain sensitivity to doxorubicin whereas luminal cancer cells did not. CONCLUSIONS: Our results suggested the prognostic value of SNRPD1 on breast cancer survival, its potential as the therapeutic target halting cell cycle progression for breast cancer control, and warranted special attention on the combined use of doxorubicin and drugs targeting SNRPD1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01932-w. BioMed Central 2021-04-20 /pmc/articles/PMC8059192/ /pubmed/33879154 http://dx.doi.org/10.1186/s12935-021-01932-w Text en © The Author(s) 2021 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 Primary Research
Dai, Xiaofeng
Yu, Lihui
Chen, Xiao
Zhang, Jianying
SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation
title SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation
title_full SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation
title_fullStr SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation
title_full_unstemmed SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation
title_short SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation
title_sort snrpd1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059192/
https://www.ncbi.nlm.nih.gov/pubmed/33879154
http://dx.doi.org/10.1186/s12935-021-01932-w
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