Selective apoptosis of breast cancer cells by siRNA targeting of BORIS.

Brother of the regulator of imprinted sites (BORIS) is an epigenetically acting transcription factor which represses the tumor inhibitor functions of the tumor suppressor protein CTCF. BORIS expression has not been documented in adult females, making it an exciting molecular target for drug development in breast cancer. Previously, we demonstrated that vaccination of mice with zing-finger (ZF)-deleted non-functional BORIS results in regression of breast cancer and generation of potent anti-tumor immune responses. RNAi induction can be used as an alternative approach for selective tumor cell killing. Short interfering RNA (siRNA) molecules targeting BORIS were generated and their efficacy was tested in MDA-MB-231 breast cancer and non-malignant epithelial cell lines. Treatment with BORIS-specific siRNA, but not control siRNA led to a concentration-dependent reduction in BORIS expression and proportional apoptotic death of the cancer but not control cells. To our knowledge this is first report demonstrating a critical role of BORIS in maintaining tumor cell viability.

Genome sequence and analysis of the oral bacterium Fusobacterium nucleatum strain ATCC 25586.

We present a complete DNA sequence and metabolic analysis of the dominant oral bacterium Fusobacterium nucleatum. Although not considered a major dental pathogen on its own, this anaerobe facilitates the aggregation and establishment of several other species including the dental pathogens Porphyromonas gingivalis and Bacteroides forsythus. The F. nucleatum strain ATCC 25586 genome was assembled from shotgun sequences and analyzed using the ERGO bioinformatics suite (http://www.integratedgenomics.com). The genome contains 2.17 Mb encoding 2,067 open reading frames, organized on a single circular chromosome with 27% GC content. Despite its taxonomic position among the gram-negative bacteria, several features of its core metabolism are similar to that of gram-positive Clostridium spp., Enterococcus spp., and Lactococcus spp. The genome analysis has revealed several key aspects of the pathways of organic acid, amino acid, carbohydrate, and lipid metabolism. Nine very-high-molecular-weight outer membrane proteins are predicted from the sequence, none of which has been reported in the literature. More than 137 transporters for the uptake of a variety of substrates such as peptides, sugars, metal ions, and cofactors have been identified. Biosynthetic pathways exist for only three amino acids: glutamate, aspartate, and asparagine. The remaining amino acids are imported as such or as di- or oligopeptides that are subsequently degraded in the cytoplasm. A principal source of energy appears to be the fermentation of glutamate to butyrate. Additionally, desulfuration of cysteine and methionine yields ammonia, H(2)S, methyl mercaptan, and butyrate, which are capable of arresting fibroblast growth, thus preventing wound healing and aiding penetration of the gingival epithelium. The metabolic capabilities of F. nucleatum revealed by its genome are therefore consistent with its specialized niche in the mouth.