Nucleolin represses transcription of the androgen receptor gene through a G-quadruplex.

Nucleolin represses transcription of the androgen receptor gene through a G-quadruplex. Oncotarget. 2020 May 12;11(19):1758-1776 Authors: Miranti CK, Moore S, Kim Y, Chappeta VR, Wu K, De B, Gokhale V, Hurley LH, Reyes-Reyes EM Abstract The androgen receptor (AR) is a major driver of prostate cancer development and progression. Men who develop advanced prostate cancer often have long-term cancer control when treated with androgen-deprivation therapies (ADT). Still, their disease inevitably becomes resistant to ADT and progresses to castration-resistant prostate cancer (CRPC). ADT involves potent competitive AR antagonists and androgen synthesis inhibitors. Resistance to these types of treatments emerges, primarily through the maintenance of AR signaling by ligand-independent activation mechanisms. There is a need to find better ways to block AR to overcome CRPC. In the findings reported here, we demonstrate that the nuclear scaffold protein, nucleolin (NCL), suppresses the expression of AR. NCL binds to a G-rich region in the AR promoter that forms a G-quadruplex (G4) structure. Binding of NCL to this G4-element is required for NCL to suppress AR expression, specifically in AR-expressing tumor cells. Compounds that stabilize G4 structures require NCL to associate with the G4-element of the AR promoter in order to decrease AR expression. A newly discovered G4 compound that suppresses AR expression demonstrates selective killing of AR-expressing tumor cells...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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