Coactivator MYST1 regulates nuclear factor-κB and androgen receptor functions during proliferation of prostate cancer...

Area of Science:

• Oncology
• Molecular Biology
• Gene Regulation

Background:

• Prostate cancer (PCa) exhibits therapeutic resistance and aggressive growth due to the synergy between androgen receptor (AR) and nuclear factor-κB (NF-κB).
• The precise mechanisms, particularly the role of coactivators in bridging AR and NF-κB functions, remain incompletely understood.

Purpose of the Study:

• To investigate the role of MYST1 (MOZ, YBF2 and SAS2, and TIP60 protein 1) in mediating the functional synergy between AR and NF-κB in prostate cancer cells.
• To elucidate the regulatory mechanisms involving MYST1, sirtuin 1, and histone acetylation in PCa progression.

Main Methods:

• Investigated MYST1's interaction with AR and NF-κB in PCa cell lines.
• Assessed the impact of NF-κB activation on MYST1 deacetylation by sirtuin 1.
• Analyzed the effect of MYST1 depletion on apoptosis (caspase 3, PARP cleavage) and cell cycle arrest (CDKN1A/p21, G2M) in AR-dependent and AR-independent PCa cells.
• Examined the influence on key cell cycle regulators and tumor protein D52 (TPD52) expression.

Main Results:

• MYST1 was found to co-stimulate AR and NF-κB functions in PCa cells.
• NF-κB activation promotes MYST1 deacetylation by sirtuin 1, which in turn regulates histone H4 acetylation.
• MYST1 depletion induced apoptosis in AR-lacking/depleted cells, but G2M arrest in AR-transformed cells, affecting cell cycle regulators and TPD52 expression.

Conclusions:

• MYST1 plays a critical role in prostate cancer progression by mediating the functional interactions between AR and NF-κB.
• The findings highlight MYST1 as a key regulator of therapeutic resistance and tumor aggressiveness in PCa.
• Targeting MYST1 interactions could offer novel therapeutic strategies for prostate cancer.