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BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy

Breast cancer 1 (BRCA1) and autophagy both play a significant role in drug resistance. However, little is known about the dynamic cross talk between BRCA1 and autophagy in the regulation of drug sensitivity. Here, we investigated the drug resistance‐associated regulation of BRCA1 in epithelial ovari...

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Autores principales: You, Yue, Bi, Fang‐Fang, Jiang, Ying, Xu, Ye‐Tao, An, Yuan‐Yuan, Li, Da, Yang, Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382722/
https://www.ncbi.nlm.nih.gov/pubmed/30636383
http://dx.doi.org/10.1002/cam4.1975
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author You, Yue
Bi, Fang‐Fang
Jiang, Ying
Xu, Ye‐Tao
An, Yuan‐Yuan
Li, Da
Yang, Qing
author_facet You, Yue
Bi, Fang‐Fang
Jiang, Ying
Xu, Ye‐Tao
An, Yuan‐Yuan
Li, Da
Yang, Qing
author_sort You, Yue
collection PubMed
description Breast cancer 1 (BRCA1) and autophagy both play a significant role in drug resistance. However, little is known about the dynamic cross talk between BRCA1 and autophagy in the regulation of drug sensitivity. Here, we investigated the drug resistance‐associated regulation of BRCA1 in epithelial ovarian cancer stem cells (EOCSCs). The results indicated that BRCA1 could regulate drug resistance in EOCSCs. Autophagy played a significant role in the stemness maintenance and was a key mechanism underlying the survival against chemotherapy in EOCSCs. Further investigation found that BRCA1 could regulate drug resistance of EOCSCs through autophagy. Meanwhile, changes in the level of autophagy provided feedback regarding the expression of BRCA1. Inhibition of autophagy activity could effectively reduce the resistance of EOCSCs caused by BRCA1. In addition, BRCA1 was able to regulate cellular apoptosis and cell cycle progression under the action of cisplatin through autophagy, indirectly affecting the drug sensitivity of EOCSCs. The present results highlight a novel relationship between BRCA1 and autophagy, which may provide insight into the etiology of BRCA1‐associated ovarian cancer, and improve our understanding of resistance mechanisms in ovarian cancer.
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spelling pubmed-63827222019-03-01 BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy You, Yue Bi, Fang‐Fang Jiang, Ying Xu, Ye‐Tao An, Yuan‐Yuan Li, Da Yang, Qing Cancer Med Clinical Cancer Research Breast cancer 1 (BRCA1) and autophagy both play a significant role in drug resistance. However, little is known about the dynamic cross talk between BRCA1 and autophagy in the regulation of drug sensitivity. Here, we investigated the drug resistance‐associated regulation of BRCA1 in epithelial ovarian cancer stem cells (EOCSCs). The results indicated that BRCA1 could regulate drug resistance in EOCSCs. Autophagy played a significant role in the stemness maintenance and was a key mechanism underlying the survival against chemotherapy in EOCSCs. Further investigation found that BRCA1 could regulate drug resistance of EOCSCs through autophagy. Meanwhile, changes in the level of autophagy provided feedback regarding the expression of BRCA1. Inhibition of autophagy activity could effectively reduce the resistance of EOCSCs caused by BRCA1. In addition, BRCA1 was able to regulate cellular apoptosis and cell cycle progression under the action of cisplatin through autophagy, indirectly affecting the drug sensitivity of EOCSCs. The present results highlight a novel relationship between BRCA1 and autophagy, which may provide insight into the etiology of BRCA1‐associated ovarian cancer, and improve our understanding of resistance mechanisms in ovarian cancer. John Wiley and Sons Inc. 2019-01-12 /pmc/articles/PMC6382722/ /pubmed/30636383 http://dx.doi.org/10.1002/cam4.1975 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the 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 Clinical Cancer Research
You, Yue
Bi, Fang‐Fang
Jiang, Ying
Xu, Ye‐Tao
An, Yuan‐Yuan
Li, Da
Yang, Qing
BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy
title BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy
title_full BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy
title_fullStr BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy
title_full_unstemmed BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy
title_short BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy
title_sort brca1 affects the resistance and stemness of skov3‐derived ovarian cancer stem cells by regulating autophagy
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382722/
https://www.ncbi.nlm.nih.gov/pubmed/30636383
http://dx.doi.org/10.1002/cam4.1975
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