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KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer

PARP inhibitors (PARPi) are currently used as first-line therapy for advanced and recurrent ovarian cancer, but the clinical efficacy is limited by drug resistance. We aimed to investigate the role of KIAA1529 in PARPi resistance in ovarian cancer. The expression of KIAA1529 was determined in ovaria...

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Detalles Bibliográficos
Autores principales: Qiao, Yuan, Yu, Xuechen, Zhou, Bo, Zhang, Kai, Huang, Juyuan, Liao, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352548/
https://www.ncbi.nlm.nih.gov/pubmed/35917645
http://dx.doi.org/10.1016/j.tranon.2022.101497
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author Qiao, Yuan
Yu, Xuechen
Zhou, Bo
Zhang, Kai
Huang, Juyuan
Liao, Jing
author_facet Qiao, Yuan
Yu, Xuechen
Zhou, Bo
Zhang, Kai
Huang, Juyuan
Liao, Jing
author_sort Qiao, Yuan
collection PubMed
description PARP inhibitors (PARPi) are currently used as first-line therapy for advanced and recurrent ovarian cancer, but the clinical efficacy is limited by drug resistance. We aimed to investigate the role of KIAA1529 in PARPi resistance in ovarian cancer. The expression of KIAA1529 was determined in ovarian cancer cells using qRT‒PCR and western blotting. Immunohistochemistry was used to examine the expression of KIAA1529 in primary ovarian cancer and recurrent ovarian cancer tissues. The effects of KIAA1529 on PARPi resistance were evaluated by knocking down KIAA1529 expression in ovarian cancer cells and assessing cell viability by CCK8 assays, apoptosis by flow cytometry, and homologous recombination (HR) repair by immunofluorescence analysis. The interaction between KIAA1529 and RAD51 was examined by western blotting. KIAA1529 was confirmed to be expressed in all ovarian cancer cell lines, and high expression of KIAA1529 was observed in recurrent ovarian cancer tissues. Inhibiting KIAA1529 expression increased the sensitivity of ovarian cancer cells to PARPi treatment. Furthermore, KIAA1529 increased the expression of the downstream effector RAD51 via Aurora-A, and HR was restored in ovarian cancer cells. This study demonstrates that KIAA1529 regulates RAD51 expression through Aurora-A to restore HR, which confers resistance to PARPi in ovarian cancer cells. These findings could provide a novel therapeutic target to overcome PARPi resistance in ovarian cancer.
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spelling pubmed-93525482022-08-09 KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer Qiao, Yuan Yu, Xuechen Zhou, Bo Zhang, Kai Huang, Juyuan Liao, Jing Transl Oncol Commentary PARP inhibitors (PARPi) are currently used as first-line therapy for advanced and recurrent ovarian cancer, but the clinical efficacy is limited by drug resistance. We aimed to investigate the role of KIAA1529 in PARPi resistance in ovarian cancer. The expression of KIAA1529 was determined in ovarian cancer cells using qRT‒PCR and western blotting. Immunohistochemistry was used to examine the expression of KIAA1529 in primary ovarian cancer and recurrent ovarian cancer tissues. The effects of KIAA1529 on PARPi resistance were evaluated by knocking down KIAA1529 expression in ovarian cancer cells and assessing cell viability by CCK8 assays, apoptosis by flow cytometry, and homologous recombination (HR) repair by immunofluorescence analysis. The interaction between KIAA1529 and RAD51 was examined by western blotting. KIAA1529 was confirmed to be expressed in all ovarian cancer cell lines, and high expression of KIAA1529 was observed in recurrent ovarian cancer tissues. Inhibiting KIAA1529 expression increased the sensitivity of ovarian cancer cells to PARPi treatment. Furthermore, KIAA1529 increased the expression of the downstream effector RAD51 via Aurora-A, and HR was restored in ovarian cancer cells. This study demonstrates that KIAA1529 regulates RAD51 expression through Aurora-A to restore HR, which confers resistance to PARPi in ovarian cancer cells. These findings could provide a novel therapeutic target to overcome PARPi resistance in ovarian cancer. Neoplasia Press 2022-07-30 /pmc/articles/PMC9352548/ /pubmed/35917645 http://dx.doi.org/10.1016/j.tranon.2022.101497 Text en © 2022 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Commentary
Qiao, Yuan
Yu, Xuechen
Zhou, Bo
Zhang, Kai
Huang, Juyuan
Liao, Jing
KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer
title KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer
title_full KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer
title_fullStr KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer
title_full_unstemmed KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer
title_short KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer
title_sort kiaa1529 regulates rad51 expression to confer parp inhibitors resistance in ovarian cancer
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352548/
https://www.ncbi.nlm.nih.gov/pubmed/35917645
http://dx.doi.org/10.1016/j.tranon.2022.101497
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