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Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor ? by XCT790 and siRNA.

ABSTRACT: Purpose:To explore the targeted therapy of estrogen-related receptor ? (ERR?) in endometrial cancer (EC) cells and its potential mechanisms. Methods:The mRNA and protein expression levels of ERR? and estrogen receptor ? (ER?) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERR?-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERR? (siRNA-ERR?), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry. After treatment with siRNA-ERR?, 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 ERR? protein levels. A higher ratio of ERa/ERRa was observed in ER?-positive RL-952 (10-fold) and ANC-3A (8.5-fold) cells, whereas a lower ratio was observed in ER?-negative HEC-1A (3.75-fold) and HEC-1B cells (0-fold). Both - exogenous XCT790 and endogenous siRNA-ERR? - can decrease the expression of ERR?, thereby inhibiting proliferation but promoting apoptosis in both ER?-positive and -negative EC cells. The XCT790 presented higher proliferation-inhibition and apoptosis rates in the ER?-positive than ER?-negative cells, whereas the siRNA-ERR? exhibited higher proliferation-inhibition and apoptosis rates in the ER?-negative than in ER?-positive cells. In total, 3 upregulated and 17 downregulated TFs were screened out by knocked-down expression of ERR? 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 ERR? provides a promising novel endocrine therapeutic strategy.

SUBMITTER: Sun P

PROVIDER: S-EPMC6089116 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA.

Sun PengMing P Mao XiaoDan X Gao Min M Huang MeiMei M Chen LiLi L Ruan GuanYu G Huang WeiYi W Braicu Elena Ioana EI Sehouli Jalid J

Cancer management and research 20180810

<h4>Purpose</h4>To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms.<h4>Methods</h4>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 ...[more]

PMID: 30127640

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Dataset Information

Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor ? by XCT790 and siRNA.

Publications

Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA.

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