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Title: JMJD6 Is a Druggable Oxygenase That Regulates AR-V7 Expression in Prostate Cancer.
Authors: Paschalis, Alec
Welti, Jonathan
Neeb, Antje J
Yuan, Wei
Figueiredo, Ines
Pereira, Rita
Ferreira, Ana
Riisnaes, Ruth
Rodrigues, Daniel Nava
Jiménez-Vacas, Juan M
Kim, Soojin
Uo, Takuma
Micco, Patrizio Di
Tumber, Anthony
Islam, Md Saiful
Moesser, Marc A
Abboud, Martine
Kawamura, Akane
Gurel, Bora
Christova, Rossitza
Gil, Veronica S
Buroni, Lorenzo
Crespo, Mateus
Miranda, Susana
Lambros, Maryou B
Carreira, Suzanne
Tunariu, Nina
Alimonti, Andrea
Al-Lazikani, Bissan
Schofield, Christopher J
Plymate, Stephen R
Sharp, Adam
de Bono, Johann S
, SU2C/PCF International Prostate Cancer Dream Team
metadata.dc.subject.mesh: Alternative Splicing
Antineoplastic Agents
Cell Line, Tumor
Cohort Studies
Enzyme Inhibitors
Gene Expression Regulation, Neoplastic
Jumonji Domain-Containing Histone Demethylases
Molecular Targeted Therapy
Prostatic Neoplasms, Castration-Resistant
Protein Isoforms
Receptors, Androgen
Retrospective Studies
Issue Date: 2021
Abstract: Endocrine resistance (EnR) in advanced prostate cancer is fatal. EnR can be mediated by androgen receptor (AR) splice variants, with AR splice variant 7 (AR-V7) arguably the most clinically important variant. In this study, we determined proteins key to generating AR-V7, validated our findings using clinical samples, and studied splicing regulatory mechanisms in prostate cancer models. Triangulation studies identified JMJD6 as a key regulator of AR-V7, as evidenced by its upregulation with in vitro EnR, its downregulation alongside AR-V7 by bromodomain inhibition, and its identification as a top hit of a targeted siRNA screen of spliceosome-related genes. JMJD6 protein levels increased (P
metadata.dc.identifier.doi: 10.1158/0008-5472.CAN-20-1807
Appears in Collections:Producción 2020

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