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Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

3β-Hydroxysteroid-Δ24 reductase (DHCR24), the final enzyme of the cholesterol biosynthetic pathway, has been associated with urogenital neoplasms. However, the function of DHCR24 in endometrial cancer (EC) remains largely elusive. Here, we analyzed the expression profile of DHCR24 and the progestero...

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Autores principales: Dai, Miao, Zhu, Xiao-Lu, Liu, Fei, Xu, Qin-Yang, Ge, Qiu-Lin, Jiang, Shu-Heng, Yang, Xiao-Mei, Li, Jun, Wang, Ya-Hui, Wu, Qing-Kai, Ai, Zhi-Hong, Teng, Yin-Cheng, Zhang, Zhi-Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256103/
https://www.ncbi.nlm.nih.gov/pubmed/28112250
http://dx.doi.org/10.1038/srep41404
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author Dai, Miao
Zhu, Xiao-Lu
Liu, Fei
Xu, Qin-Yang
Ge, Qiu-Lin
Jiang, Shu-Heng
Yang, Xiao-Mei
Li, Jun
Wang, Ya-Hui
Wu, Qing-Kai
Ai, Zhi-Hong
Teng, Yin-Cheng
Zhang, Zhi-Gang
author_facet Dai, Miao
Zhu, Xiao-Lu
Liu, Fei
Xu, Qin-Yang
Ge, Qiu-Lin
Jiang, Shu-Heng
Yang, Xiao-Mei
Li, Jun
Wang, Ya-Hui
Wu, Qing-Kai
Ai, Zhi-Hong
Teng, Yin-Cheng
Zhang, Zhi-Gang
author_sort Dai, Miao
collection PubMed
description 3β-Hydroxysteroid-Δ24 reductase (DHCR24), the final enzyme of the cholesterol biosynthetic pathway, has been associated with urogenital neoplasms. However, the function of DHCR24 in endometrial cancer (EC) remains largely elusive. Here, we analyzed the expression profile of DHCR24 and the progesterone receptor (PGR) in our tissue microarray of EC (n = 258), the existing EC database in GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas). We found that DHCR24 was significantly elevated in patients with EC, and that the up-regulation of DHCR24 was associated with advanced clinical stage, histological grading, vascular invasion, lymphatic metastasis, and reduced overall survival. In addition, DHCR24 expression could be induced by insulin though STAT3, which directly binds to the promoter elements of DHCR24, as demonstrated by ChIP-PCR and luciferase assays. Furthermore, genetically silencing DHCR24 inhibited the metastatic ability of endometrial cancer cells and up-regulated PGR expression, which made cells more sensitive to progestin. Taken together, we have demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss.
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spelling pubmed-52561032017-01-24 Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma Dai, Miao Zhu, Xiao-Lu Liu, Fei Xu, Qin-Yang Ge, Qiu-Lin Jiang, Shu-Heng Yang, Xiao-Mei Li, Jun Wang, Ya-Hui Wu, Qing-Kai Ai, Zhi-Hong Teng, Yin-Cheng Zhang, Zhi-Gang Sci Rep Article 3β-Hydroxysteroid-Δ24 reductase (DHCR24), the final enzyme of the cholesterol biosynthetic pathway, has been associated with urogenital neoplasms. However, the function of DHCR24 in endometrial cancer (EC) remains largely elusive. Here, we analyzed the expression profile of DHCR24 and the progesterone receptor (PGR) in our tissue microarray of EC (n = 258), the existing EC database in GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas). We found that DHCR24 was significantly elevated in patients with EC, and that the up-regulation of DHCR24 was associated with advanced clinical stage, histological grading, vascular invasion, lymphatic metastasis, and reduced overall survival. In addition, DHCR24 expression could be induced by insulin though STAT3, which directly binds to the promoter elements of DHCR24, as demonstrated by ChIP-PCR and luciferase assays. Furthermore, genetically silencing DHCR24 inhibited the metastatic ability of endometrial cancer cells and up-regulated PGR expression, which made cells more sensitive to progestin. Taken together, we have demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss. Nature Publishing Group 2017-01-23 /pmc/articles/PMC5256103/ /pubmed/28112250 http://dx.doi.org/10.1038/srep41404 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Dai, Miao
Zhu, Xiao-Lu
Liu, Fei
Xu, Qin-Yang
Ge, Qiu-Lin
Jiang, Shu-Heng
Yang, Xiao-Mei
Li, Jun
Wang, Ya-Hui
Wu, Qing-Kai
Ai, Zhi-Hong
Teng, Yin-Cheng
Zhang, Zhi-Gang
Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma
title Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma
title_full Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma
title_fullStr Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma
title_full_unstemmed Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma
title_short Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma
title_sort cholesterol synthetase dhcr24 induced by insulin aggravates cancer invasion and progesterone resistance in endometrial carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256103/
https://www.ncbi.nlm.nih.gov/pubmed/28112250
http://dx.doi.org/10.1038/srep41404
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