TY - JOUR
T1 - Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma
AU - Chen, Ruichao
AU - Zhang, Minfen
AU - Liu, Wenya
AU - Chen, Hui
AU - Cai, Tonghui
AU - Xiong, Hanzhen
AU - Sheng, Xiujie
AU - Liu, Shaoyan
AU - Peng, Juan
AU - Wang, Fang
AU - Chen, Hao
AU - Lin, Wanrun
AU - Xu, Xuehu
AU - Zheng, Wenxin
AU - Jiang, Qingping
N1 - Funding Information:
This study was supported by Scientific Research Grant from the national natural scientific foundation of China (No. 81602289); the Guangdong Science and Technology Department (No. 2013B021800193, No. 2016ZC0139), The Health and Family Planning Commission of Guangzhou Municipality (No. 20151A010107), Western medicine guide project of Guangzhou Municipal Health Bureau (No. 20151A010103) and a Scientific Research Grant from the Third Affiliated Hospital of Guangzhou Medical University (No. 2014Y10, No. 2017Q03). The funder had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
Publisher Copyright:
© 2018, The Author(s).
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1038/s41419-018-1207-4
DO - 10.1038/s41419-018-1207-4
M3 - Article
C2 - 30584245
AN - SCOPUS:85058916907
SN - 2041-4889
VL - 10
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 1
M1 - 4
ER -