title: Nicotinamide adenine dinucleotide (NAD) may affect DNA methyltransferase 1 through regulation of BRCA1 in ovarian cancer.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Fang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Bi
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Harvard Medical School Boston, MA 02115, USA.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Zhou
authors.affiliation: Division of Cell Signaling, National Institute for Physiological Sciences Okazaki 444-8787, Japan.
authors.forename: Wu-Ping
authors.initials: WP
authors.lastname: Sun
authors.affiliation: Department of Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College Beijing 100005, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University Shenyang 110001, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Da
authors.initials: D
authors.lastname: Li
keywords: BRCA1; DNMT1; NAD; ovarian cancer