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Rad50 promotes ovarian cancer progression through NF‐κB activation

Rad50 is a component of MRN (Mre11‐Rad50‐Nbs1), which participates in DNA double‐strand break repair and DNA‐damage checkpoint activation. Here, we sought to investigate the clinical and functional significance of Rad50 in high‐grade serous ovarian cancer (HGSOC). We found that Rad50 was frequently...

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Autores principales: Li, Yinuo, Wang, Shourong, Li, Peng, Li, Yingwei, Liu, Yao, Fang, Haiya, Zhang, Xiyu, Liu, Zhaojian, Kong, Beihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642684/
https://www.ncbi.nlm.nih.gov/pubmed/34734468
http://dx.doi.org/10.1111/jcmm.17017
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author Li, Yinuo
Wang, Shourong
Li, Peng
Li, Yingwei
Liu, Yao
Fang, Haiya
Zhang, Xiyu
Liu, Zhaojian
Kong, Beihua
author_facet Li, Yinuo
Wang, Shourong
Li, Peng
Li, Yingwei
Liu, Yao
Fang, Haiya
Zhang, Xiyu
Liu, Zhaojian
Kong, Beihua
author_sort Li, Yinuo
collection PubMed
description Rad50 is a component of MRN (Mre11‐Rad50‐Nbs1), which participates in DNA double‐strand break repair and DNA‐damage checkpoint activation. Here, we sought to investigate the clinical and functional significance of Rad50 in high‐grade serous ovarian cancer (HGSOC). We found that Rad50 was frequently upregulated in HGSOCs and enhanced Rad50 expression inversely correlated with patient survival. In addition, ectopic expression of Rad50 promoted proliferation/invasion and induced EMT of ovarian cancer cells, whereas knockdown of Rad50 led to decreased aggressive behaviors. Mechanistic investigations revealed that Rad50 induced aggressiveness in HGSOC via activation of NF‐κB signaling pathway. Moreover, we identified CARD9 as an interacting protein of Rad50 in ovarian cancer cells and the activation of NF‐κB pathway by Rad50 is CARD9 dependent. Our findings provide evidence that Rad50 exhibits oncogenic property via NF‐κB activation in HGSOC.
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spelling pubmed-86426842021-12-15 Rad50 promotes ovarian cancer progression through NF‐κB activation Li, Yinuo Wang, Shourong Li, Peng Li, Yingwei Liu, Yao Fang, Haiya Zhang, Xiyu Liu, Zhaojian Kong, Beihua J Cell Mol Med Original Articles Rad50 is a component of MRN (Mre11‐Rad50‐Nbs1), which participates in DNA double‐strand break repair and DNA‐damage checkpoint activation. Here, we sought to investigate the clinical and functional significance of Rad50 in high‐grade serous ovarian cancer (HGSOC). We found that Rad50 was frequently upregulated in HGSOCs and enhanced Rad50 expression inversely correlated with patient survival. In addition, ectopic expression of Rad50 promoted proliferation/invasion and induced EMT of ovarian cancer cells, whereas knockdown of Rad50 led to decreased aggressive behaviors. Mechanistic investigations revealed that Rad50 induced aggressiveness in HGSOC via activation of NF‐κB signaling pathway. Moreover, we identified CARD9 as an interacting protein of Rad50 in ovarian cancer cells and the activation of NF‐κB pathway by Rad50 is CARD9 dependent. Our findings provide evidence that Rad50 exhibits oncogenic property via NF‐κB activation in HGSOC. John Wiley and Sons Inc. 2021-11-03 2021-12 /pmc/articles/PMC8642684/ /pubmed/34734468 http://dx.doi.org/10.1111/jcmm.17017 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Li, Yinuo
Wang, Shourong
Li, Peng
Li, Yingwei
Liu, Yao
Fang, Haiya
Zhang, Xiyu
Liu, Zhaojian
Kong, Beihua
Rad50 promotes ovarian cancer progression through NF‐κB activation
title Rad50 promotes ovarian cancer progression through NF‐κB activation
title_full Rad50 promotes ovarian cancer progression through NF‐κB activation
title_fullStr Rad50 promotes ovarian cancer progression through NF‐κB activation
title_full_unstemmed Rad50 promotes ovarian cancer progression through NF‐κB activation
title_short Rad50 promotes ovarian cancer progression through NF‐κB activation
title_sort rad50 promotes ovarian cancer progression through nf‐κb activation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642684/
https://www.ncbi.nlm.nih.gov/pubmed/34734468
http://dx.doi.org/10.1111/jcmm.17017
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