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Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double‐strand breaks

TNKS1BP1 is a member of the poly(ADP‐ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in hum...

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Autores principales: Tan, Wei, Guan, Hua, Zou, Lian‐Hong, Wang, Yu, Liu, Xiao‐Dan, Rang, Wei‐Qing, Zhou, Ping‐Kun, Pei, Hua‐Dong, Zhong, Cai‐Gao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313643/
https://www.ncbi.nlm.nih.gov/pubmed/28058814
http://dx.doi.org/10.1002/cam4.995
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author Tan, Wei
Guan, Hua
Zou, Lian‐Hong
Wang, Yu
Liu, Xiao‐Dan
Rang, Wei‐Qing
Zhou, Ping‐Kun
Pei, Hua‐Dong
Zhong, Cai‐Gao
author_facet Tan, Wei
Guan, Hua
Zou, Lian‐Hong
Wang, Yu
Liu, Xiao‐Dan
Rang, Wei‐Qing
Zhou, Ping‐Kun
Pei, Hua‐Dong
Zhong, Cai‐Gao
author_sort Tan, Wei
collection PubMed
description TNKS1BP1 is a member of the poly(ADP‐ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in human lung adenocarcinoma (LAC) tissues, and was associated with poor overall survival (OS) in LAC patients. Dysregulation of TNKS1BP1 affected the sensitivity of A549 cells to several DNA damage agents including cisplatin, bleomycin, and ionizing radiation. Mechanically, overexpression of TNKS1BP1 increased the accumulation of S phase cells, which was accompanied by a decrease in M phase cells. More importantly, we found TNKS1BP1 regulated genome stability, mainly through affecting the homologous recombination pathway of DNA double‐strand breaks by inhibiting the RAD51 foci formation. Overall, our study indicates that, in LAC, aberrant expressions of TNKS1BP1 are common events, and overexpression of TNKS1BP1 might affect outcomes of cancer patients to chemotherapy and radiotherapy.
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spelling pubmed-53136432017-02-24 Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double‐strand breaks Tan, Wei Guan, Hua Zou, Lian‐Hong Wang, Yu Liu, Xiao‐Dan Rang, Wei‐Qing Zhou, Ping‐Kun Pei, Hua‐Dong Zhong, Cai‐Gao Cancer Med Cancer Biology TNKS1BP1 is a member of the poly(ADP‐ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in human lung adenocarcinoma (LAC) tissues, and was associated with poor overall survival (OS) in LAC patients. Dysregulation of TNKS1BP1 affected the sensitivity of A549 cells to several DNA damage agents including cisplatin, bleomycin, and ionizing radiation. Mechanically, overexpression of TNKS1BP1 increased the accumulation of S phase cells, which was accompanied by a decrease in M phase cells. More importantly, we found TNKS1BP1 regulated genome stability, mainly through affecting the homologous recombination pathway of DNA double‐strand breaks by inhibiting the RAD51 foci formation. Overall, our study indicates that, in LAC, aberrant expressions of TNKS1BP1 are common events, and overexpression of TNKS1BP1 might affect outcomes of cancer patients to chemotherapy and radiotherapy. John Wiley and Sons Inc. 2017-01-06 /pmc/articles/PMC5313643/ /pubmed/28058814 http://dx.doi.org/10.1002/cam4.995 Text en © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Tan, Wei
Guan, Hua
Zou, Lian‐Hong
Wang, Yu
Liu, Xiao‐Dan
Rang, Wei‐Qing
Zhou, Ping‐Kun
Pei, Hua‐Dong
Zhong, Cai‐Gao
Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double‐strand breaks
title Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double‐strand breaks
title_full Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double‐strand breaks
title_fullStr Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double‐strand breaks
title_full_unstemmed Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double‐strand breaks
title_short Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double‐strand breaks
title_sort overexpression of tnks1bp1 in lung cancers and its involvement in homologous recombination pathway of dna double‐strand breaks
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313643/
https://www.ncbi.nlm.nih.gov/pubmed/28058814
http://dx.doi.org/10.1002/cam4.995
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