Abstract
BackgroundOrphan nuclear receptor estrogen related receptor β (Esrrb or ERRβ) is well known in stem cells and early embryonic development. However, little is known about its function in cancer.MethodWe investigated the mRNA profile alterations induced by Esrrb expression and its synthetic ligand DY131 in human prostate cancer DU145 cells via RNA-Seq analysis.ResultsWe distinguished 67 mRNAs differentially expressed by Esrrb alone. Although DY131 alone did not change any gene, treatment of DY131 in the presence of Esrrb altered 1161 mRNAs. These observations indicated Esrrb had both ligand-independent and ligand-dependent activity. When Esrrb was expressed, DY131 treatment further regulated 15 Esrrb-altered mRNAs. DY131 acted as an antagonist for 11 of 15 mRNAs (wdr52, f13a1, pxdn, spns2, loc100506599, tagln, loc441454, tkel1, sema3f, zcwpw2, sdc2) and as an agonist for 4 of the 15 mRNAs (rarres3, oasl, padi2, ddx60). Gene ontology analyses showed altered genes are related to transcription and translation regulation, cell proliferation and apoptosis regulation, and cellular metabolism.ConclusionOur results characterized mRNA profiles in DU145 prostate cancer cells driven by Esrrb expression and Esrrb ligand DY131, and provided multiple markers to characterize Esrrb’s function in Esrrb research.Electronic supplementary materialThe online version of this article (doi:10.1186/s12867-015-0049-1) contains supplementary material, which is available to authorized users.
Highlights
Orphan nuclear receptor estrogen related receptor β (Esrrb or ERRβ) is well known in stem cells and early embryonic development
estrogen related receptor beta (Esrrb) acts as a transcription factor by binding to a specific DNA sequence estrogen related receptor response element (ERRE), which is known as steroid factor response element (SFRE), or half site estrogen response element [1, 2]
Establishment of the Esrrb stably transfected DU145 cells Esrrb expression vector or control pcDNA3.1 (Zeo+) vector were transfected into DU145 cells
Summary
Orphan nuclear receptor estrogen related receptor β (Esrrb or ERRβ) is well known in stem cells and early embryonic development. Esrrb acts as a transcription factor by binding to a specific DNA sequence estrogen related receptor response element (ERRE), which is known as steroid factor response element (SFRE), or half site estrogen response element [1, 2]. Though early studies showed a very limited range of tissues with positive Esrrb expression, recent studies reported that short. Esrrb was shown to be down-regulated in prostate cancer epithelium compared to normal prostate tissue [8,9,10]. Esrrb can inhibit Estrogen Receptor transcriptional activity in uterine endometrial cancer cells and Nrf2-Keap signaling pathway in breast cancer cells [11, 12]
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