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NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression

BACKGROUND: NUDT21, an RNA binding protein, has been reported to play an important role in the regulation of multiple biological responses. Detection of NUDT21 expression may lead to the identification of a novel marker for breast cancer. PURPOSE: The aim of this study was to investigate the clinica...

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Autores principales: Wang, Bi-Jun, Liu, Da-Chao, Guo, Qian-Ying, Han, Xiao-Wen, Bi, Xiao-Min, Wang, Hao, Wu, Zheng-Sheng, Wu, Wen-Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200255/
https://www.ncbi.nlm.nih.gov/pubmed/32431549
http://dx.doi.org/10.2147/CMAR.S239664
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author Wang, Bi-Jun
Liu, Da-Chao
Guo, Qian-Ying
Han, Xiao-Wen
Bi, Xiao-Min
Wang, Hao
Wu, Zheng-Sheng
Wu, Wen-Yong
author_facet Wang, Bi-Jun
Liu, Da-Chao
Guo, Qian-Ying
Han, Xiao-Wen
Bi, Xiao-Min
Wang, Hao
Wu, Zheng-Sheng
Wu, Wen-Yong
author_sort Wang, Bi-Jun
collection PubMed
description BACKGROUND: NUDT21, an RNA binding protein, has been reported to play an important role in the regulation of multiple biological responses. Detection of NUDT21 expression may lead to the identification of a novel marker for breast cancer. PURPOSE: The aim of this study was to investigate the clinical significance and functional role of NUDT21 in breast cancer. METHODS: The protein expression of NUDT21 was examined by immunohistochemistry (IHC) in 100 paraffin-embedded, archived breast cancer samples and 100 benign breast tissues. Then, the correlations between the NUDT21 expression and clinicopathologic characteristics and prognoses of the breast cancer patients were analyzed. In addition, the function of NUDT21 in breast cancer cell lines was detected by the methyl thiazolyl tetrazolium, colony formation and transwell assays. Finally, mass spectrometry analysis and Western blotting were used to identify the proteins that interact directly with NUDT21. RESULTS: IHC analysis revealed that the expression of NUDT21 was significantly lower in breast cancer tissues compared with benign breast disease tissues. The correlation analysis revealed that low expression of NUDT21 was positively correlated with tumor size, lymph node metastasis, and TNM stage. Also, Kaplan–Meier survival curves showed that patients with lower NUDT21 expression had shorter overall survival and relapse-free survival compared with higher NUDT21 expression. In addition, the knockdown of NUDT21 enhanced cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Consistently, the overexpression of NUDT21 inhibited cell proliferation, migration, invasion, and EMT. In addition, NUDT21 directly interacted with CPSF6 and negatively regulated its expression. Moreover, the knockdown of CPSF6 reversed NUDT21 expression-induced cancer cell migration and invasion. CONCLUSION: NUDT21 might play a tumor-suppressive role by inhibiting cell proliferation and invasion via the NUDT21/CPSF6 signaling pathway in breast cancer cells.
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spelling pubmed-72002552020-05-19 NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression Wang, Bi-Jun Liu, Da-Chao Guo, Qian-Ying Han, Xiao-Wen Bi, Xiao-Min Wang, Hao Wu, Zheng-Sheng Wu, Wen-Yong Cancer Manag Res Original Research BACKGROUND: NUDT21, an RNA binding protein, has been reported to play an important role in the regulation of multiple biological responses. Detection of NUDT21 expression may lead to the identification of a novel marker for breast cancer. PURPOSE: The aim of this study was to investigate the clinical significance and functional role of NUDT21 in breast cancer. METHODS: The protein expression of NUDT21 was examined by immunohistochemistry (IHC) in 100 paraffin-embedded, archived breast cancer samples and 100 benign breast tissues. Then, the correlations between the NUDT21 expression and clinicopathologic characteristics and prognoses of the breast cancer patients were analyzed. In addition, the function of NUDT21 in breast cancer cell lines was detected by the methyl thiazolyl tetrazolium, colony formation and transwell assays. Finally, mass spectrometry analysis and Western blotting were used to identify the proteins that interact directly with NUDT21. RESULTS: IHC analysis revealed that the expression of NUDT21 was significantly lower in breast cancer tissues compared with benign breast disease tissues. The correlation analysis revealed that low expression of NUDT21 was positively correlated with tumor size, lymph node metastasis, and TNM stage. Also, Kaplan–Meier survival curves showed that patients with lower NUDT21 expression had shorter overall survival and relapse-free survival compared with higher NUDT21 expression. In addition, the knockdown of NUDT21 enhanced cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Consistently, the overexpression of NUDT21 inhibited cell proliferation, migration, invasion, and EMT. In addition, NUDT21 directly interacted with CPSF6 and negatively regulated its expression. Moreover, the knockdown of CPSF6 reversed NUDT21 expression-induced cancer cell migration and invasion. CONCLUSION: NUDT21 might play a tumor-suppressive role by inhibiting cell proliferation and invasion via the NUDT21/CPSF6 signaling pathway in breast cancer cells. Dove 2020-05-01 /pmc/articles/PMC7200255/ /pubmed/32431549 http://dx.doi.org/10.2147/CMAR.S239664 Text en © 2020 Wang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Wang, Bi-Jun
Liu, Da-Chao
Guo, Qian-Ying
Han, Xiao-Wen
Bi, Xiao-Min
Wang, Hao
Wu, Zheng-Sheng
Wu, Wen-Yong
NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression
title NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression
title_full NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression
title_fullStr NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression
title_full_unstemmed NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression
title_short NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression
title_sort nudt21 suppresses breast cancer tumorigenesis through regulating cpsf6 expression
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200255/
https://www.ncbi.nlm.nih.gov/pubmed/32431549
http://dx.doi.org/10.2147/CMAR.S239664
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