BAP18, as a corepressor of AR together with the SIN3A/HDAC complex, promotes AR-positive triple-negative breast cancer progression.

BACKGROUND: Triple-negative breast cancer (TNBC) is considered a highly heterogeneous disease. Androgen receptor (AR)-positive TNBC is a subtype with distinct molecular features. However, the molecular mechanism underlying the modulation of the AR signaling pathway in TNBC is still elusive. RESULTS: BPTF-associated protein of 18 kDa (BAP18) was significantly upregulated in AR-positive TNBC samples and was positively correlated with advanced disease stage and poor prognosis. BAP18 was shown to act as a transcriptional corepressor of AR in AR-positive TNBC cells and is involved in the promotion of AR-positive TNBC. Mechanically, BAP18 associates with AR and the SIN3A/HDAC subcomplex. BAP18 facilitates the recruitment of SIN3A/HDAC to androgen response elements (AREs) in the promoter regions of P21 and PTEN, subsequently leading to a reduced level of histone H4 acetylation on AREs. CONCLUSION: Our study revealed that BAP18, which acts as a novel AR corepressor, is involved in AR-positive TNBC progression, suggesting that BAP18 could be a potential therapeutic target for AR-positive TNBC patients.