TNRC9 (TOX3) downregulates BRCA1 expression and promotes breast cancer aggressiveness

Background: Although the linkage between germline mutations of BRCA1 and hereditary breast/ovarian cancers is well established, recent evidence suggests that altered expression of wild type BRCA1 might contribute to the sporadic forms of breast cancer. The mechanism underlying the downregulation BRCA1 expression is not well understood. It might be dependent upon repressor activity that governs histone acetylation and DNA accessibility at the BRCA1 promoter. TNRC9 (TOX3) gene, highly associated with breast cancer susceptibility, encodes a nuclear protein of uncertain function but can modify chromatin structure. We hypothesized that constitutive expression of TNRC9 could be relevant to breast cancer biology through the modulation of BRCA1 activity. Methods: We assessed the associations of TNRC9 gene amplification with breast cancer onset and survival. The search for targets and effects of TNRC9 was performed using multifaceted molecular approaches. Results: The TNRC9 gene is often amplified and overexpresse...