ABSTRACT
Androgen receptor (AR) is a ligand-responsive transcription factor that drives terminal differentiation of the prostatic luminal epithelia. By contrast, in tumors originating from these cells, AR chromatin occupancy is extensively reprogrammed to activate malignant phenotypes, the molecular mechanisms of which remain unknown. Here, we show that tumor-specific AR enhancers are critically reliant on H3K36 dimethyltransferase activity of NSD2. NSD2 expression is abnormally induced in prostate cancer, where its inactivation impairs AR transactivation potential by disrupting over 65% of its cistrome. NSD2-dependent AR sites distinctively harbor the chimeric FOXA1:AR half-motif, which exclusively comprise tumor-specific AR enhancer circuitries defined from patient specimens. NSD2 inactivation also engenders increased dependency on the NSD1 paralog, and a dual NSD1/2 PROTAC degrader is preferentially cytotoxic in AR-dependent prostate cancer models. Altogether, we characterize NSD2 as an essential AR neo-enhanceosome subunit that enables its oncogenic activity, and position NSD1/2 as viable co-targets in advanced prostate cancer.
ABSTRACT
The performances of polybenzimidazole (PBI) and polysulfone (PSF) membranes for recovering water from reverse osmosis (RO) reject of brackish water through forward osmosis (FO) were assessed and compared. Non-functionalised multi-walled carbon nanotubes (MWCNT) were added to the membrane casting solutions, with concentrations ranging from 0 to 3 wt%. The experiment was conducted for eight samples using RO reject of brackish water as the feed solution (FS) and 2 M analytical grade MgCl2 as the draw solution (DS). The hydrophilicity, water permeability, salt rejection rate (Rs), water flux (WF) and porosity of the membranes improved with increasing MWCNT content up to 2 wt%. Also, the structural parameter, salt permeability and reverse solute flux decreased. PBI/MWCNT2 wt% exhibited the best performance among the membranes tested compared with porosity of 70 ± 4 %, structural parameter of 0.36 ± 0.2 µm, and Rs of 93.5 %. In contrast with the pristine PBI membrane, an average water flux enhancement of 15 % and 49 % was observed for the FS and DS sides, respectively, for PBI/MWCNT2 wt%. It is evident from the results that including MWCNT improves the performance of both membranes, with better relative performance for PBI membranes than PSF membranes.