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Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma
Endometrial carcinoma is one of the most common malignancies in the female reproductive system. It is well-known that estrogen plays an important role in the pathogenesis of endometrioid endometrial carcinoma (EEC), and induces the cancer suppressor gene PTEN deletion. However, how estrogen affects...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315040/ https://www.ncbi.nlm.nih.gov/pubmed/30584245 http://dx.doi.org/10.1038/s41419-018-1207-4 |
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author | Chen, Ruichao Zhang, Minfen Liu, Wenya Chen, Hui Cai, Tonghui Xiong, Hanzhen Sheng, Xiujie Liu, Shaoyan Peng, Juan Wang, Fang Chen, Hao Lin, Wanrun Xu, Xuehu Zheng, Wenxin Jiang, Qingping |
author_facet | Chen, Ruichao Zhang, Minfen Liu, Wenya Chen, Hui Cai, Tonghui Xiong, Hanzhen Sheng, Xiujie Liu, Shaoyan Peng, Juan Wang, Fang Chen, Hao Lin, Wanrun Xu, Xuehu Zheng, Wenxin Jiang, Qingping |
author_sort | Chen, Ruichao |
collection | PubMed |
description | Endometrial carcinoma is one of the most common malignancies in the female reproductive system. It is well-known that estrogen plays an important role in the pathogenesis of endometrioid endometrial carcinoma (EEC), and induces the cancer suppressor gene PTEN deletion. However, how estrogen affects PTEN expression remains unknown. In the present study, we found in 40 EEC specimens, miR-200c level was higher in most cancer areas than that in the adjacent normal endometrium, while PTEN and PTENP1 were lower. Moreover, the expression of PTEN/PTENP1 and miR-200c also showed a converse relationship in EEC cell lines. In addition, we demonstrated that miR-200c bound directly to PTEN and PTENP1, and PTENP1 could reverse miR-200c inhibition function to PTEN using a dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays. Next, 17β-estradiol (E2) treatment could improve miR-200c and drop the PTEN level, which caused a consequential increase of the phospho-PI3K-AKT pathway genes. When we stably knocked down estrogen receptor α (ERα) expression in the EEC cell line, the effects of E2 on miR-200c and PTEN declined. In addition, it was demonstrated that E2 might modulate cell proliferation, migration and invasion relying on the expression of miR-200c. Taken together, it can be concluded that estrogen improves the miR-200c level by combining with ER, PTENP1 and PTEN could be inhibited by miR-200c, and then activate the PI3K-AKT pathway. This work provided a new mechanism of EEC development and a new potential therapeutic target. |
format | Online Article Text |
id | pubmed-6315040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63150402019-01-03 Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma Chen, Ruichao Zhang, Minfen Liu, Wenya Chen, Hui Cai, Tonghui Xiong, Hanzhen Sheng, Xiujie Liu, Shaoyan Peng, Juan Wang, Fang Chen, Hao Lin, Wanrun Xu, Xuehu Zheng, Wenxin Jiang, Qingping Cell Death Dis Article Endometrial carcinoma is one of the most common malignancies in the female reproductive system. It is well-known that estrogen plays an important role in the pathogenesis of endometrioid endometrial carcinoma (EEC), and induces the cancer suppressor gene PTEN deletion. However, how estrogen affects PTEN expression remains unknown. In the present study, we found in 40 EEC specimens, miR-200c level was higher in most cancer areas than that in the adjacent normal endometrium, while PTEN and PTENP1 were lower. Moreover, the expression of PTEN/PTENP1 and miR-200c also showed a converse relationship in EEC cell lines. In addition, we demonstrated that miR-200c bound directly to PTEN and PTENP1, and PTENP1 could reverse miR-200c inhibition function to PTEN using a dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays. Next, 17β-estradiol (E2) treatment could improve miR-200c and drop the PTEN level, which caused a consequential increase of the phospho-PI3K-AKT pathway genes. When we stably knocked down estrogen receptor α (ERα) expression in the EEC cell line, the effects of E2 on miR-200c and PTEN declined. In addition, it was demonstrated that E2 might modulate cell proliferation, migration and invasion relying on the expression of miR-200c. Taken together, it can be concluded that estrogen improves the miR-200c level by combining with ER, PTENP1 and PTEN could be inhibited by miR-200c, and then activate the PI3K-AKT pathway. This work provided a new mechanism of EEC development and a new potential therapeutic target. Nature Publishing Group UK 2018-12-18 /pmc/articles/PMC6315040/ /pubmed/30584245 http://dx.doi.org/10.1038/s41419-018-1207-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Chen, Ruichao Zhang, Minfen Liu, Wenya Chen, Hui Cai, Tonghui Xiong, Hanzhen Sheng, Xiujie Liu, Shaoyan Peng, Juan Wang, Fang Chen, Hao Lin, Wanrun Xu, Xuehu Zheng, Wenxin Jiang, Qingping Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma |
title | Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma |
title_full | Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma |
title_fullStr | Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma |
title_full_unstemmed | Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma |
title_short | Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma |
title_sort | estrogen affects the negative feedback loop of ptenp1-mir200c to inhibit pten expression in the development of endometrioid endometrial carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315040/ https://www.ncbi.nlm.nih.gov/pubmed/30584245 http://dx.doi.org/10.1038/s41419-018-1207-4 |
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