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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Messenger RNA profile analysis deciphers new Esrrb responsive genes in prostate cancer cells
Yuan Lu1,2,3, Jilong Li4,5,6, Jianlin Cheng7,8,9
1Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA. y_l54@txstate.edu.
Background:
Orphan 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.
Method:
We investigated the mRNA profile alterations induced by Esrrb expression and its synthetic ligand DY131 in human prostate cancer DU145 cells via RNA-Seq analysis.
Results:
We 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.
Conclusion:
Our 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.
Insights
Estrogen related receptor beta (Esrrb) influences gene expression in prostate cancer cells, with its ligand DY131 showing both agonist and antagonist activity. This research identifies key mRNA markers for Esrrb function in cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- Estrogen related receptor beta (Esrrb) is crucial in stem cells and early development.
- Its role in cancer, particularly prostate cancer, remains largely uncharacterized.
Purpose of the Study:
- To investigate the impact of Esrrb expression and its synthetic ligand DY131 on mRNA profiles in human prostate cancer cells.
- To elucidate the ligand-dependent and ligand-independent activities of Esrrb in the context of cancer.
Main Methods:
- RNA-sequencing (RNA-Seq) was employed to analyze global mRNA expression changes.
- Human prostate cancer DU145 cells were utilized to assess Esrrb and DY131 effects.
Main Results:
- Esrrb expression alone altered 67 mRNAs, indicating ligand-independent activity.
- DY131, in the presence of Esrrb, significantly altered 1161 mRNAs, demonstrating ligand-dependent activity.
- DY131 acted as an antagonist for 11 and an agonist for 4 of the 15 Esrrb-regulated mRNAs, affecting pathways like transcription, translation, proliferation, apoptosis, and metabolism.
Conclusions:
- The study characterized comprehensive mRNA profiles in DU145 prostate cancer cells modulated by Esrrb and its ligand DY131.
- Identified multiple mRNA markers that can be used to further research Esrrb's function in cancer biology.
