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Knockdown of CYP24A1 Aggravates 1α,25(OH)(2)D(3)-Inhibited Migration and Invasion of Mouse Ovarian Epithelial Cells by Suppressing EMT

Epithelial-mesenchymal transition (EMT) bestows cancer cells with motile and invasive properties. But for ovarian tissues, EMT plays a physiological role in the postovulatory repair of ovary surface epithelial (OSE) cells. Accumulating data indicated that 1α,25(OH)(2)D(3) decreased both the migratio...

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Autores principales: Wang, Ping, Xu, Jiming, You, Weijing, Hou, Yongfeng, Wang, Shuiliang, Ma, Yujie, Tan, Jianming, Zhang, Zengli, Hu, Wentao, Li, Bingyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403498/
https://www.ncbi.nlm.nih.gov/pubmed/32850381
http://dx.doi.org/10.3389/fonc.2020.01258
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author Wang, Ping
Xu, Jiming
You, Weijing
Hou, Yongfeng
Wang, Shuiliang
Ma, Yujie
Tan, Jianming
Zhang, Zengli
Hu, Wentao
Li, Bingyan
author_facet Wang, Ping
Xu, Jiming
You, Weijing
Hou, Yongfeng
Wang, Shuiliang
Ma, Yujie
Tan, Jianming
Zhang, Zengli
Hu, Wentao
Li, Bingyan
author_sort Wang, Ping
collection PubMed
description Epithelial-mesenchymal transition (EMT) bestows cancer cells with motile and invasive properties. But for ovarian tissues, EMT plays a physiological role in the postovulatory repair of ovary surface epithelial (OSE) cells. Accumulating data indicated that 1α,25(OH)(2)D(3) decreased both the migration and invasion of various cancer cells by suppressing EMT. However, it remains unclear whether 1α,25(OH)(2)D(3) inhibits the process of EMT during different stages of oncogenic transformation in mouse OSE (MOSE) cells. In present study, a spontaneous malignant transformation model of MOSE cells at three sequential stages (early, intermediate and late) was established in vitro first and then subjected to 1α,25(OH)(2)D(3) treatment to investigate the effect of 1α,25(OH)(2)D(3) on the oncogenic transformation of MOSE cells. We found that 1α,25(OH)(2)D(3) significantly reduced the proliferation and invasion of late malignant transformed MOSE (M-L cells) cells by inhibiting EMT both in vitro and in vivo, but not in intermediate transformed (M-I) cells. Importantly, we found that the levels of CYP24A1 in M-I cells were dramatically higher than that in M-L cells following treatment with 1α,25(OH)(2)D(3). Furthermore, we demonstrated that, in both M-I and M-L cells with CYP24A1 knockdown, 1α,25(OH)(2)D(3) suppressed the proliferation and invasion, and reduced the expression of N-cadherin, Vimentin, β-catenin and Snail. In addition, knockdown of CYP24A1 suppressed EMT by increasing E-cadherin while decreasing N-cadherin, Vimentin, β-catenin and Snail. These findings provide support for inhibiting CYP24A1 as a potential approach to activate the vitamin D pathway in the prevention and therapy of ovarian cancer.
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spelling pubmed-74034982020-08-25 Knockdown of CYP24A1 Aggravates 1α,25(OH)(2)D(3)-Inhibited Migration and Invasion of Mouse Ovarian Epithelial Cells by Suppressing EMT Wang, Ping Xu, Jiming You, Weijing Hou, Yongfeng Wang, Shuiliang Ma, Yujie Tan, Jianming Zhang, Zengli Hu, Wentao Li, Bingyan Front Oncol Oncology Epithelial-mesenchymal transition (EMT) bestows cancer cells with motile and invasive properties. But for ovarian tissues, EMT plays a physiological role in the postovulatory repair of ovary surface epithelial (OSE) cells. Accumulating data indicated that 1α,25(OH)(2)D(3) decreased both the migration and invasion of various cancer cells by suppressing EMT. However, it remains unclear whether 1α,25(OH)(2)D(3) inhibits the process of EMT during different stages of oncogenic transformation in mouse OSE (MOSE) cells. In present study, a spontaneous malignant transformation model of MOSE cells at three sequential stages (early, intermediate and late) was established in vitro first and then subjected to 1α,25(OH)(2)D(3) treatment to investigate the effect of 1α,25(OH)(2)D(3) on the oncogenic transformation of MOSE cells. We found that 1α,25(OH)(2)D(3) significantly reduced the proliferation and invasion of late malignant transformed MOSE (M-L cells) cells by inhibiting EMT both in vitro and in vivo, but not in intermediate transformed (M-I) cells. Importantly, we found that the levels of CYP24A1 in M-I cells were dramatically higher than that in M-L cells following treatment with 1α,25(OH)(2)D(3). Furthermore, we demonstrated that, in both M-I and M-L cells with CYP24A1 knockdown, 1α,25(OH)(2)D(3) suppressed the proliferation and invasion, and reduced the expression of N-cadherin, Vimentin, β-catenin and Snail. In addition, knockdown of CYP24A1 suppressed EMT by increasing E-cadherin while decreasing N-cadherin, Vimentin, β-catenin and Snail. These findings provide support for inhibiting CYP24A1 as a potential approach to activate the vitamin D pathway in the prevention and therapy of ovarian cancer. Frontiers Media S.A. 2020-07-29 /pmc/articles/PMC7403498/ /pubmed/32850381 http://dx.doi.org/10.3389/fonc.2020.01258 Text en Copyright © 2020 Wang, Xu, You, Hou, Wang, Ma, Tan, Zhang, Hu and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wang, Ping
Xu, Jiming
You, Weijing
Hou, Yongfeng
Wang, Shuiliang
Ma, Yujie
Tan, Jianming
Zhang, Zengli
Hu, Wentao
Li, Bingyan
Knockdown of CYP24A1 Aggravates 1α,25(OH)(2)D(3)-Inhibited Migration and Invasion of Mouse Ovarian Epithelial Cells by Suppressing EMT
title Knockdown of CYP24A1 Aggravates 1α,25(OH)(2)D(3)-Inhibited Migration and Invasion of Mouse Ovarian Epithelial Cells by Suppressing EMT
title_full Knockdown of CYP24A1 Aggravates 1α,25(OH)(2)D(3)-Inhibited Migration and Invasion of Mouse Ovarian Epithelial Cells by Suppressing EMT
title_fullStr Knockdown of CYP24A1 Aggravates 1α,25(OH)(2)D(3)-Inhibited Migration and Invasion of Mouse Ovarian Epithelial Cells by Suppressing EMT
title_full_unstemmed Knockdown of CYP24A1 Aggravates 1α,25(OH)(2)D(3)-Inhibited Migration and Invasion of Mouse Ovarian Epithelial Cells by Suppressing EMT
title_short Knockdown of CYP24A1 Aggravates 1α,25(OH)(2)D(3)-Inhibited Migration and Invasion of Mouse Ovarian Epithelial Cells by Suppressing EMT
title_sort knockdown of cyp24a1 aggravates 1α,25(oh)(2)d(3)-inhibited migration and invasion of mouse ovarian epithelial cells by suppressing emt
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403498/
https://www.ncbi.nlm.nih.gov/pubmed/32850381
http://dx.doi.org/10.3389/fonc.2020.01258
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