A comprehensive microarray analysis of hepatocellular carcinoma (HCC) revealed distinct synexpression patterns during intrahepatic metastasis. Recent evidence has demonstrated that synexpression group member genes are likely to be regulated by master control gene(s). Here we investigate the functions and gene regulation of the transcription factor SOX4 in intrahepatic metastatic HCC. SOX4 is important in tumor metastasis as RNAi knockdown reduces tumor cell migration, invasion, in vivo tumorigenesis and metastasis. A multifaceted approach integrating gene profiling, binding site computation and empirical verification by chromatin immunoprecipitation and gene ablation refined the consensus SOX4 binding motif and identified 32 binding loci in 31 genes with high confidence. RNAi knockdown of two SOX4 target genes, neuropilin 1 and semaphorin 3C, drastically reduced cell migration activity in HCC cell lines suggesting that SOX4 exerts some of its action via regulation of these two downstream targets. The discovery of 31 previously unidentified targets expands our knowledge of how SOX4 modulates HCC progression and implies a range of novel SOX4 functions. This integrated approach sets a paradigm whereby a subset of member genes from a synexpression group can be regulated by one master control gene and this is exemplified by SOX4 and advanced HCC.
In the presence of catalytic amounts of CeCl 3.7H 2O, [RuCl(benzene)(S)-SunPhos]Cl is a highly effective catalyst for the asymmetric hydrogenation of aromatic alpha-ketoesters. A variety of ethyl alpha-hydroxy-alpha-arylacetates have been prepared in up to 98.3% ee with a TON up to 10,000. Challenging aromatic alpha-ketoesters with ortho substituents are also hydrogenated with high enantioselectivities. The addition of CeCl 3.7H 2O not only improves the enantioselectivity but also enhances the stability of the catalyst. The ratio of CeCl 3.7H 2O to [RuCl(benzene)(S)-SunPhos]Cl plays an important role in the hydrogenation reaction with a large substrate/catalyst ratio.
An efficient Pd-catalyzed Sonogashira coupling reaction was achieved in the absence of a copper salt or amine with an inorganic base and easily prepared, air-stable aminophosphine ligands in commonly used organic solvents; good to excellent yields were obtained. Under optimized reaction conditions, the Sonogashira coupling reaction occurred selectively when an enyne substrate was employed and no Heck reaction product was detected; acetone-masked acetylene and trimethylsilylacetylene can also be efficiently coupled, providing a method to make terminal alkynes.
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