Abstract
Nicotinamide adenine dinucleotide (NAD) is a crucial molecule of energy production and signal transduction processes that have been linked to ovarian cancer development. Notably, emerging evidence has led to considerable interest in the role of DNA methyltransferase 1 (DNMT1) in the initiation and progression of ovarian cancer. However, dynamic crosstalk between NAD and DNMT1 is poorly understood. Here, we show that DNMT1 levels are upregulated, along with increased NAD levels in non-BRCA1-mutated ovarian cancer cells. In contrast, DNMT1 levels are not affected by increasing NAD levels in BRCA1-mutated ovarian cancer cells. Mechanistically, BRCA1 inactivity-mediated loss of H3K9ac enrichment around the core promoter inhibits DNMT1 transcription. Consistent with this, BRCA1 levels correlate with DNMT1 levels (R = 0.534, R < 0.001) in human ovarian cancer specimens. Therefore, these results highlight a novel regulatory effect of NAD on DNMT1, and further correlate the physiological properties of NAD metabolism with DNMT1-mediated biological processes. All of this may improve our understanding of the basic molecular mechanism underlying NAD- and DNMT1-related ovarian cancer progression.