Search

In rats, prepubertal exposure to low-fat diet containing n-3 polyunsaturated fatty acids (PUFA) reduces mammary cell proliferation, increases apoptosis, and lowers risk of mammary tumors in adulthood, whereas prepubertal high-fat n-3 PUFA exposure has opposite effects. To identify signaling pathways mediating these effects, we performed gene microarray analyses and determined protein levels of genes related to mammary epithelial cell proliferation. Nursing female rats and rat pups were fed low-fat (16% energy from fat) or high-fat (39% energy from fat) n-3 or n-6 PUFA diets between postnatal days 5 and 24. cDNA gene expression microarrays were used to identify global changes in the mammary glands of 50-day-old rats. Differences in gene expression were confirmed by real-time quantitative PCR, and immunohistochemistry was used to assess changes in the peroxisome proliferator-activated receptor gamma and cyclin D1 levels. DNA damage was determined by 8-hydroxy-2'-deoxyguanosine assay. Expressions of the antioxidant genes thioredoxin, heme oxygenase, NADP-dependent isocitrate dehydrogenase, and metallothionein III, as well as peroxisome proliferator-activated receptor gamma protein, were increased in the mammary glands of 50-day-old rats prepubertally fed the low-fat n-3 PUFA diet. Prepubertal exposure to the high-fat n-3 PUFA diet increased DNA damage and cyclin D1 protein and reduced expression of BRCA1 and cardiotrophin-1. Reduction in mammary tumorigenesis among rats prepubertally fed a low-fat n-3 PUFA diet was associated with an up-regulation of antioxidant genes, whereas the increase in mammary tumorigenesis in the high-fat n-3 PUFA fed rats was linked to up-regulation of genes that induce cell proliferation and down-regulation of genes that repair DNA damage and induce apoptosis.

Unlabelled: The NCBI Gene Expression Omnibus (GEO) represents the largest public repository of microarray data. However, finding data in GEO can be challenging. We have developed GEOmetadb in an attempt to make querying the GEO metadata both easier and more powerful. All GEO metadata records as well as the relationships between them are parsed and stored in a local MySQL database. A powerful, flexible web search interface with several convenient utilities provides query capabilities not available via NCBI tools. In addition, a Bioconductor package, GEOmetadb that utilizes a SQLite export of the entire GEOmetadb database is also available, rendering the entire GEO database accessible with full power of SQL-based queries from within R., Availability: The web interface and SQLite databases available at http://gbnci.abcc.ncifcrf.gov/geo/. The Bioconductor package is available via the Bioconductor project. The corresponding MATLAB implementation is also available at the same website.

Osteosarcoma is the most common type of bone cancer in children and adolescents. Impaired differentiation of osteoblast cells is a distinguishing feature of this aggressive disease. As improvements in survival outcomes have largely plateaued, better understanding of the bone differentiation program may provide new treatment approaches. The miRNA cluster miR-23a~27a~24-2, particularly miR-23a, has been shown to interact with genes important for bone development. However, global changes in gene expression associated with functional gain of this cluster have not been fully explored. To better understand the relationship between miR-23a expression and bone cell differentiation, we carried out a large-scale gene expression analysis in HOS cells. Experimental results demonstrate that over-expression of miR-23a delays differentiation in this system. Downstream bioinformatic analysis identified miR-23a target gene connexin-43 (Cx43/GJA1), a mediator of intercellular signaling critical to osteoblast development, as acutely affected by miR-23a levels. Connexin-43 is up-regulated in the course of HOS cell differentiation and is down-regulated in cells transfected with miR-23a. Analysis of gene expression data, housed at Gene Expression Omnibus, reveals that Cx43 is consistently up-regulated during osteoblast differentiation. Suppression of Cx43 mRNA by miR-23a was confirmed in vitro using a luciferase reporter assay. This work demonstrates novel interactions between microRNA expression, intercellular signaling and bone differentiation in osteosarcoma. [ABSTRACT FROM AUTHOR]

Cell cycle is a cellular process that is subject to stringent control. In contrast to the wealth of knowledge of proteins controlling the cell cycle, very little is known about the molecular role of lncRNAs (long noncoding RNAs) in cell-cycle progression. By performing genome-wide transcriptome analyses in cell-cycle-synchronized cells, we observed cell-cycle phase-specific induction of >2000 lncRNAs. Further, we demonstrate that an S-phase-upregulated lncRNA, SUNO1, facilitates cell-cycle progression by promoting YAP1-mediated gene expression. SUNO1 facilitates the cell-cycle-specific transcription of WTIP, a positive regulator of YAP1, by promoting the co-activator, DDX5-mediated stabilization of RNA polymerase II on chromatin. Finally, elevated SUNO1 levels are associated with poor cancer prognosis and tumorigenicity, implying its pro-survival role. Thus, we demonstrate the role of a S-phase up-regulated lncRNA in cell-cycle progression via modulating the expression of genes controlling cell proliferation. [ABSTRACT FROM AUTHOR]

• In all, 39 RsNRT genes are systematically identified at genome-wide level in radish. • A range of RsNRTs exhibit significant differential expression under abiotic stresses. • RsNRT1.1a may play a critical role in root NO 3 − uptake under low-nitrogen condition. Radish is an important economical vegetable crop that requires adequate nitrogen supply for taproot formation and enlargement. Nitrate transporter (NRT) family represents a key gatekeeper in modulating nitrogen uptake and utilization in plants. However, the comprehensive characterization of the NRT gene family remains largely unexplored in radish. Herein, a total of 39 RsNRT genes were identified from the radish genome, which were unevenly distributed onto eight chromosomes except Chr3. Phylogenetic analysis indicated that the NRT1 and NRT2 subfamily members from radish, Arabidopsis and Brassica rapa were classified into Cluster I and Cluster II, indicating that the NRT proteins were relatively conserved in the Brassicaceae family. A range of cis -regulatory elements (e.g. AuxRE, ABRE and LTR) in the promoter of RsNRTs were involved in phytohormone and abiotic stress response. Transcriptome-based expression analysis indicated that several RsNRTs showed differential expression under heat, salt or heavy metal stresses. RT-qPCR analysis revealed that six RsNRT genes, including RsNRT1.1a, RsNRT1.2a, RsNRT1.5a, RsNRT2.1b, RsNRT2.2a and RsNRT2.3b , exhibited significantly up-regulated expression under NO 3 − deficiency condition. Notably, the expression of RsNRT1.1a was significantly increased in both the 'NAU-WXQ' (low-N-sensitive) and 'NAU-ZYQ' (low-N-tolerant) genotypes under 5 mM NO 3 − treatment, indicating that it might act as a critical participator in root NO 3 − uptake under low-N supply condition. These results would provide fundamental basis to decipher the molecular mechanisms underlying RsNRT -mediated N absorption and translocation in radish. [ABSTRACT FROM AUTHOR]

Radish (Raphanus sativus L.) is an important cool-season root vegetable crop worldwide. Heat stress (HS) severely restricts radish taproot formation and diminishes its yield and quality. Although WRKY transcription factors (TFs) play pivotal roles in several biotic and/or abiotic stress responses, how WRKY TFs mediate HS regulatory network remains elusive in radish. Herein, a WRKY-Ia TF gene, RsWRKY26 , exhibited dramatically up-regulated expression under heat stress, especially at 8 h and 24 h. RsWRKY26 was localized to the nucleus and displayed transactivation activity in both the yeast and plant cells. Interestingly, the RsWRKY26- overexpressing radish plants exhibited significantly enhanced thermotolerance compared to the control plants, whereas its knock-down plants showed increased thermosensitivity. Both in vitro and in vivo assays showed that RsWRKY26 activated RsHSP70–20 transcription by directly binding to the specific W-box element in its promoter. Moreover, several biochemical assays revealed that a VQ motif-containing protein RsVQ4 interacted with RsWRKY26, which promoted DNA-binding activity of RsWRKY26 to regulate RsHSP70–20 expression. Notably, RsWRKY26 in turn binds to RsVQ4 promoter to activate its transcription, thereby forming a positive feedback loop to cooperatively regulate heat stress response in radish. Together, we revealed a novel RsVQ4-RsWRKY26- RsHSP70–20 module to promote the thermotolerance, which would facilitate dissecting the molecular regulatory network of RsWRKY-mediated thermal morphogenesis in radish. • RsWRKY26 positively regulates thermotolerance by activating RsHSP70-20 transcription. • RsVQ4 physically interacts with RsWRKY26 to promote its DNA-binding activity. • RsWRKY26 binds to RsVQ4 promoter to form a feedback loop enhancing thermotolerance. [ABSTRACT FROM AUTHOR]