AbstractBromodomain testis-specific factor (BRDT) is a member of the bromodomain and extra-terminal (BET) family proteins. Its expression and potential functions in ovarian cancer were examined. We show that BRDT is overexpressed in human ovarian cancer tissues and in established (CaOV3)/primary ovarian cancer cells. However, its expression is low in ovarian epithelial tissues and cells. Significantly, shRNA-induced silencing or CRISPR/Cas9-mediated knockout of BRDT inhibited ovarian cancer cell growth, viability, proliferation and migration, and induced significant apoptosis activation. Conversely, exogenous overexpression of BRDT, by a lentiviral construct, augmented CaOV3 cell proliferation and migration. In CaOV3 cells expression of two key BRDT target genes, polo-like kinase 1 (PLK1) and aurora kinase C (AURKC), was downregulated by BRDT shRNA or knockout, but upregulated with BRDT overexpression. In vivo, xenograft tumors-derived from BRDT-knockout CaOV3 cells grew significantly slower than control tumors in severe combined immunodeficient (SCID) mice. Furthermore, intratumoral injection of BRDT shRNA lentivirus potently inhibited the growth of primary ovarian cancer xenografts in SCID mice. Downregulation of PLK1 and AURKC was detected in BRDT-knockout and BRDT-silenced tumor tissues. Collectively, BRDT overexpression promotes ovarian cancer cell progression. Targeting BRDT could be a novel strategy to treat ovarian cancer.
Leptin stimulates ovarian cancer cell growth and inhibits apoptosis by increasing cyclin D1 and Mcl-1 expression via the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways
