A high-density consensus linkage map of white lupin highlights synteny with narrow-leafed lupin and provides markers tagging key agronomic traits.

White lupin (Lupinus albus L.) is a valuable source of seed protein, carbohydrates and oil, but requires genetic improvement to attain its agronomic potential. This study aimed to (i) develop a new high-density consensus linkage map based on new, transcriptome-anchored markers; (ii) map four important agronomic traits, namely, vernalization requirement, seed alkaloid content, and resistance to anthracnose and Phomopsis stem blight; and, (iii) define regions of synteny between the L. albus and narrow-leafed lupin (L. angustifolius L.) genomes. Mapping of white lupin quantitative trait loci (QTLs) revealed polygenic control of vernalization responsiveness and anthracnose resistance, as well as a single locus regulating seed alkaloid content. We found high sequence collinearity between white and narrow-leafed lupin genomes. Interestingly, the white lupin QTLs did not correspond to previously mapped narrow-leafed lupin loci conferring vernalization independence, anthracnose resistance, low alkaloids and Phomopsis stem blight resistance, highlighting different genetic control of these traits. Our suite of allele-sequenced and PCR validated markers tagging these QTLs is immediately applicable for marker-assisted selection in white lupin breeding. The consensus map constitutes a platform for synteny-based gene cloning approaches and can support the forthcoming white lupin genome sequencing efforts.

Depletion of OLFM4 gene inhibits cell growth and increases sensitization to hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric cancer cells.

BACKGROUND: Human olfactomedin 4 (OLFM4) gene is a secreted glycoprotein more commonly known as the anti-apoptotic molecule GW112. OLFM4 is found to be frequently up-regulated in many types of human tumors including gastric cancer and it was believed to play significant role in the progression of gastric cancer. Although the function of OLFM4 has been indicated in many studies, recent evidence strongly suggests a cell or tissue type-dependent role of OLFM4 in cell growth and apoptosis. The aim of this study is to examine the role of gastric cancer-specific expression of OLFM4 in cell growth and apoptosis resistance. METHODS: OLFM4 expression was eliminated by RNA interference in SGC-7901 and MKN45 cells. Cell proliferation, anchorage-independent growth, cell cycle and apoptosis were characterized in vitro. Tumorigenicity was analyzed in vivo. The apoptosis and caspase-3 activation in response to hydrogen peroxide (H2O2) or tumor necrosis factor-alpha (TNF α) were assessed in the presence or absence of caspase inhibitor Z-VAD-fmk. RESULTS: The elimination of OLFM4 protein by RNA interference in SGC-7901 and MKN45 cells significantly inhibits tumorigenicity both in vitro and in vivo by induction of cell G1 arrest (all P < 0.01). OLFM4 knockdown did not trigger obvious cell apoptosis but increased H2O2 or TNF α-induced apoptosis and caspase-3 activity (all P < 0.01). Treatment of Z-VAD-fmk attenuated caspase-3 activity and significantly reversed the H(2)O(2) or TNF α-induced apoptosis in OLFM4 knockdown cells (all P < 0.01). CONCLUSION: Our study suggests that depletion of OLFM4 significantly inhibits tumorigenicity of the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can sensitize gastric cancer cells to H2O2 or TNF α treatment by increasing caspase-3 dependent apoptosis. A combination strategy based on OLFM4 inhibition and anticancer drugs treatment may provide therapeutic potential in gastric cancer intervention.

Gene silence-induced downregulation of survivin inhibits bladder cancer cells.

Urinary bladder cancer accounts for approximately 3% of all cancers in humans. Treatment for urinary bladder is not satisfactory. The present study aims to elucidate the effect of gene silencing of survivin on the inhibition of bladder cancer cells. In this study, we constructed survivin shRNA-carrying lentiviral vectors. Bladder cancer cell lines, T24 cells and BJ cells, were transduced with the constructed shRNA of survivin. The frequency of apoptotic bladder cancer cells was assessed by flow cytometry. The results showed that transfection with survivin shRNA significantly inhibited cell proliferation of both T24 and BJ cells. Most T24 and BJ cells accumulated at the G2/M stage; a portion of them was at sub-G1 stage. An increase in the fraction of bladder cancer cells undergoing apoptosis was noted. Among eight apoptosis-associated proteins, the amounts of BAX and BAD were significantly increased in the survivin-deficient bladder cancer cells. The findings suggest that survivin may be a therapeutic target of bladder cancer to selectively inhibit cell proliferation of bladder cancer cells.

WITHDRAWN: Survivin knock down by short hairpin RNA inhibits proliferation and induces apoptosis in EJ bladder cancer cells.

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