Abstract 2036: Overcoming platinum-resistance in ovarian cancer via targeting basonuclin1 (BNC1)

Purpose This study aims to interrogate if basonuclin1 (BNC1), a key gene identified through integrative TCGA-based functional genomic analysis, is a relevant target for overcoming chemo-resistance in high-grade serous ovarian cancer (HGS-OvCa). BNC1 is a transcription factor which can regulate ribosomal biogenesis and cell proliferation. Methods TCGA mRNA expression and clinical response data were used to systematically identify genes associated with chemo-resistance in patients with HGS-OvCa. Gene-specific effects were subsequently studied for selected targets in vitro. BNC1 targeted siRNA was used to study the functional role of BNC1 in chemo-resistance. Apoptosis and cell cycle analyses were carried out following BNC1 silencing in ovarian cancer cell lines with or without the presence of cisplatin. The in vivo effects of silencing BNC1 on the chemosensitivity were tested using an orthotopic mouse model (A2780CP20) of ovarian cancer. Results The expression of BNC1 was found to be increased by more than two-fold (Agilent platform; p