Targeting Feedforward Loops Formed by Nuclear Receptor RORγ and Kinase PBK in mCRPC with Hyperactive AR Signaling
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. RORγ Antagonist/Inverse Agonist cmpd 31 Ootently Inhibits CRPC Cell Survival, Migration, and Invasion
2.2. Orally Administered RORγ Antagonists/Inverse Agonists Potently Inhibit Growth of PDX Tumors
2.3. RORγ Antagonists/Inverse Agonists Suppress the Expression of Gene Programs Linked to Tumor Aggressiveness
2.4. PBK Is a Downstream Target of RORγ
2.5. PBK Interacts With RORγ and Modulates RORγ Protein Stability
2.6. Dual Inhibition of PBK and RORγ Synergistically Inhibits CRPC Cell Survival and Invasion and AR Signaling
3. Discussion
4. Materials and Methods
4.1. Cell Culture and siRNA Transfection
4.2. Chemicals and Reagents
4.3. Cell Viability and Growth Assay
4.4. Western Blotting and qRT-PCR
4.5. Immunohistochemistry (IHC)
4.6. Transwell Assay
4.7. Lentivirus Production, Cell Infection, co-IP, and Ubiquitin Pull Down
4.8. Xenograft Tumor Models and Treatments
4.9. RNA-Seq and Bioinformatics Analysis
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Zhang, X.; Huang, Z.; Wang, J.; Ma, Z.; Yang, J.; Corey, E.; Evans, C.P.; Yu, A.-M.; Chen, H.-W. Targeting Feedforward Loops Formed by Nuclear Receptor RORγ and Kinase PBK in mCRPC with Hyperactive AR Signaling. Cancers 2021, 13, 1672. https://doi.org/10.3390/cancers13071672
Zhang X, Huang Z, Wang J, Ma Z, Yang J, Corey E, Evans CP, Yu A-M, Chen H-W. Targeting Feedforward Loops Formed by Nuclear Receptor RORγ and Kinase PBK in mCRPC with Hyperactive AR Signaling. Cancers. 2021; 13(7):1672. https://doi.org/10.3390/cancers13071672
Chicago/Turabian StyleZhang, Xiong, Zenghong Huang, Junjian Wang, Zhao Ma, Joy Yang, Eva Corey, Christopher P. Evans, Ai-Ming Yu, and Hong-Wu Chen. 2021. "Targeting Feedforward Loops Formed by Nuclear Receptor RORγ and Kinase PBK in mCRPC with Hyperactive AR Signaling" Cancers 13, no. 7: 1672. https://doi.org/10.3390/cancers13071672