Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA
PengMing Sun,1,* XiaoDan Mao,1,* Min Gao,2 MeiMei Huang,1 LiLi Chen,1 GuanYu Ruan,1 WeiYi Huang,1 Elena Ioana Braicu,3 Jalid Sehouli3 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, P...
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doaj-e0996da1168249eea00ed12db1759a9e2020-11-25T00:14:30ZengDove Medical PressCancer Management and Research1179-13222018-08-01Volume 102521253539803Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNASun PMMao XDGao MHuang MMChen LLRuan GYHuang WYBraicu EISehouli JPengMing Sun,1,* XiaoDan Mao,1,* Min Gao,2 MeiMei Huang,1 LiLi Chen,1 GuanYu Ruan,1 WeiYi Huang,1 Elena Ioana Braicu,3 Jalid Sehouli3 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, People’s Republic of China; 2Department of Gynecology Oncology, Beijing Cancer Hospital, Beijing 100142, People’s Republic of China; 3Department of Gynecology, Campus Virchow Clinic, Charité Medical University Berlin, Berlin, Germany *These authors contributed equally to this work Purpose: To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms.Methods: The mRNA and protein expression levels of ERRα and estrogen receptor α (ERα) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERRα-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERRα (siRNA-ERRα), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry. After treatment with siRNA-ERRα, the expression profiles of transcription factors (TFs) were analyzed by protein/DNA arrays in EC cells.Results: The relative mRNA levels of ERRa in RL-952 (1±0.0831) and AN3-CA (1.162±0.0325) were significantly higher than those in HEC-1A (0.3081±0.0339) and HEC-1B (0.1119±0.0091) (P<0.05), and similar results were observed for ERRα protein levels. A higher ratio of ERa/ERRa was observed in ERα-positive RL-952 (10-fold) and ANC-3A (8.5-fold) cells, whereas a lower ratio was observed in ERα-negative HEC-1A (3.75-fold) and HEC-1B cells (0-fold). Both – exogenous XCT790 and endogenous siRNA-ERRa – can decrease the expression of ERRα, thereby inhibiting proliferation but promoting apoptosis in both ERα-positive and -negative EC cells. The XCT790 presented higher proliferation-inhibition and apoptosis rates in the ERα-positive than ERα-negative cells, whereas the siRNA-ERRα exhibited higher proliferation-inhibition and apoptosis rates in the ERα-negative than in ERα-positive cells. In total, 3 upregulated and 17 downregulated TFs were screened out by knocked-down expression of ERRα in all EC cells. Among them, the upregulated TFs organic cation transporter 3/4(Oct3/4), hepatic nuclear factor 4 (HNF4), HNF4 and chicken ovalbumin upstream TF (COUP-TF) as well as downregulated transcription factor EB (TFEB) were found to be statistically significant (P<0.05). Conclusion: Targeting ERRα provides a promising novel endocrine therapeutic strategy. Keywords: ERRα, XCT790, siRNA, endocrine target therapy, endometrial cancer cellshttps://www.dovepress.com/novel-endocrine-therapeutic-strategy-in-endometrial-carcinoma-targetin-peer-reviewed-article-CMARERRαXCT790siRNAEndocrine target therapyEndometrial cancer cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sun PM Mao XD Gao M Huang MM Chen LL Ruan GY Huang WY Braicu EI Sehouli J |
spellingShingle |
Sun PM Mao XD Gao M Huang MM Chen LL Ruan GY Huang WY Braicu EI Sehouli J Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA Cancer Management and Research ERRα XCT790 siRNA Endocrine target therapy Endometrial cancer cells |
author_facet |
Sun PM Mao XD Gao M Huang MM Chen LL Ruan GY Huang WY Braicu EI Sehouli J |
author_sort |
Sun PM |
title |
Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA |
title_short |
Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA |
title_full |
Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA |
title_fullStr |
Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA |
title_full_unstemmed |
Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA |
title_sort |
novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by xct790 and sirna |
publisher |
Dove Medical Press |
series |
Cancer Management and Research |
issn |
1179-1322 |
publishDate |
2018-08-01 |
description |
PengMing Sun,1,* XiaoDan Mao,1,* Min Gao,2 MeiMei Huang,1 LiLi Chen,1 GuanYu Ruan,1 WeiYi Huang,1 Elena Ioana Braicu,3 Jalid Sehouli3 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, People’s Republic of China; 2Department of Gynecology Oncology, Beijing Cancer Hospital, Beijing 100142, People’s Republic of China; 3Department of Gynecology, Campus Virchow Clinic, Charité Medical University Berlin, Berlin, Germany *These authors contributed equally to this work Purpose: To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms.Methods: The mRNA and protein expression levels of ERRα and estrogen receptor α (ERα) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERRα-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERRα (siRNA-ERRα), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry. After treatment with siRNA-ERRα, the expression profiles of transcription factors (TFs) were analyzed by protein/DNA arrays in EC cells.Results: The relative mRNA levels of ERRa in RL-952 (1±0.0831) and AN3-CA (1.162±0.0325) were significantly higher than those in HEC-1A (0.3081±0.0339) and HEC-1B (0.1119±0.0091) (P<0.05), and similar results were observed for ERRα protein levels. A higher ratio of ERa/ERRa was observed in ERα-positive RL-952 (10-fold) and ANC-3A (8.5-fold) cells, whereas a lower ratio was observed in ERα-negative HEC-1A (3.75-fold) and HEC-1B cells (0-fold). Both – exogenous XCT790 and endogenous siRNA-ERRa – can decrease the expression of ERRα, thereby inhibiting proliferation but promoting apoptosis in both ERα-positive and -negative EC cells. The XCT790 presented higher proliferation-inhibition and apoptosis rates in the ERα-positive than ERα-negative cells, whereas the siRNA-ERRα exhibited higher proliferation-inhibition and apoptosis rates in the ERα-negative than in ERα-positive cells. In total, 3 upregulated and 17 downregulated TFs were screened out by knocked-down expression of ERRα in all EC cells. Among them, the upregulated TFs organic cation transporter 3/4(Oct3/4), hepatic nuclear factor 4 (HNF4), HNF4 and chicken ovalbumin upstream TF (COUP-TF) as well as downregulated transcription factor EB (TFEB) were found to be statistically significant (P<0.05). Conclusion: Targeting ERRα provides a promising novel endocrine therapeutic strategy. Keywords: ERRα, XCT790, siRNA, endocrine target therapy, endometrial cancer cells |
topic |
ERRα XCT790 siRNA Endocrine target therapy Endometrial cancer cells |
url |
https://www.dovepress.com/novel-endocrine-therapeutic-strategy-in-endometrial-carcinoma-targetin-peer-reviewed-article-CMAR |
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