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MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers

Chemo-resistance is an important barrier to effective treatment of ovarian cancer. Poly (ADP-ribose) polymerase (PARP) inhibitors are currently promising targeted drugs used to treat BRCA-mutant ovarian cancer. Ovarian cancer patients with BRCA 1/2 mutations appear to benefit better from PARP inhibi...

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Autores principales: Sun, Yue, Wu, Jing, Dong, Xiaoying, Zhang, Jingzi, Meng, Chao, Liu, Guoyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770486/
https://www.ncbi.nlm.nih.gov/pubmed/33360300
http://dx.doi.org/10.1016/j.tranon.2020.100987
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author Sun, Yue
Wu, Jing
Dong, Xiaoying
Zhang, Jingzi
Meng, Chao
Liu, Guoyan
author_facet Sun, Yue
Wu, Jing
Dong, Xiaoying
Zhang, Jingzi
Meng, Chao
Liu, Guoyan
author_sort Sun, Yue
collection PubMed
description Chemo-resistance is an important barrier to effective treatment of ovarian cancer. Poly (ADP-ribose) polymerase (PARP) inhibitors are currently promising targeted drugs used to treat BRCA-mutant ovarian cancer. Ovarian cancer patients with BRCA 1/2 mutations appear to benefit better from PARP inhibitors and chemotherapy. Understanding the mechanisms underlying PARP inhibitors and chemotherapy resistance is urgently needed. There is increasing evidence that microRNAs (miRNAs) are involved in drug resistance. MiR-506-3p is an effective inhibitor of the epithelial-to-mesenchymal transition (EMT), and can enhance chemotherapy and olaparib response in high-grade serous ovarian cancer (HGS-OvCa). Enhancer of Zeste Homolog 2 (EZH2) is considered as a direct target of miR-506-3p. The silencing of EZH2 mimics the inhibitory effects of miR-506-3p on chemo-resistance and olaparib response. Rescue of EZH2 prevented the functions of miR-506-3p. Moreover, EZH2 activates the β-catenin pathway. MiR-506-3p overexpression decreased the level of β-catenin, and the sensitivity to olaparib and cisplatin mediated by miR-506-3p was partially reversed by regulating β-catenin expression in ovarian cancer. Our results suggest that miR-506-3p increases response to PARP inhibitors and cisplatin in serous ovarian cancer by targeting EZH2/β-catenin signal pathway, which opens the possibility of using miR-506-3p overexpression as a potential therapeutic for ovarian cancer.
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spelling pubmed-77704862021-01-08 MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers Sun, Yue Wu, Jing Dong, Xiaoying Zhang, Jingzi Meng, Chao Liu, Guoyan Transl Oncol Original Research Chemo-resistance is an important barrier to effective treatment of ovarian cancer. Poly (ADP-ribose) polymerase (PARP) inhibitors are currently promising targeted drugs used to treat BRCA-mutant ovarian cancer. Ovarian cancer patients with BRCA 1/2 mutations appear to benefit better from PARP inhibitors and chemotherapy. Understanding the mechanisms underlying PARP inhibitors and chemotherapy resistance is urgently needed. There is increasing evidence that microRNAs (miRNAs) are involved in drug resistance. MiR-506-3p is an effective inhibitor of the epithelial-to-mesenchymal transition (EMT), and can enhance chemotherapy and olaparib response in high-grade serous ovarian cancer (HGS-OvCa). Enhancer of Zeste Homolog 2 (EZH2) is considered as a direct target of miR-506-3p. The silencing of EZH2 mimics the inhibitory effects of miR-506-3p on chemo-resistance and olaparib response. Rescue of EZH2 prevented the functions of miR-506-3p. Moreover, EZH2 activates the β-catenin pathway. MiR-506-3p overexpression decreased the level of β-catenin, and the sensitivity to olaparib and cisplatin mediated by miR-506-3p was partially reversed by regulating β-catenin expression in ovarian cancer. Our results suggest that miR-506-3p increases response to PARP inhibitors and cisplatin in serous ovarian cancer by targeting EZH2/β-catenin signal pathway, which opens the possibility of using miR-506-3p overexpression as a potential therapeutic for ovarian cancer. Neoplasia Press 2020-12-22 /pmc/articles/PMC7770486/ /pubmed/33360300 http://dx.doi.org/10.1016/j.tranon.2020.100987 Text en © 2020 The Authors http://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 Original Research
Sun, Yue
Wu, Jing
Dong, Xiaoying
Zhang, Jingzi
Meng, Chao
Liu, Guoyan
MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers
title MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers
title_full MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers
title_fullStr MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers
title_full_unstemmed MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers
title_short MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers
title_sort microrna-506-3p increases the response to parp inhibitors and cisplatin by targeting ezh2/β-catenin in serous ovarian cancers
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770486/
https://www.ncbi.nlm.nih.gov/pubmed/33360300
http://dx.doi.org/10.1016/j.tranon.2020.100987
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