Nevertheless, a study by Yu et al. has revealed that another combination of four factors (Oct3/4, Sox2, NANOG [Nanog ho-meobox], and LIN28 [lin-28 homolog]) is also sufficient to induce pluripotent stem cells from human somatic cells, 4 indicating that more genes are involved in the establishment or maintenance of pluripotency. In this case, the therapy of HCC directing to one or several of these genes may be insufficient to achieve satisfactory efficacy. On the other hand, a recent report by Gupta et al. showed that salinomycin might selectively eliminate breast CSCs and inhibit metastasis by inducing the differentiation of CSCs. They also suggest that it is preferable to treat cancer using agents that target both the CSCs and non-CSCs, because non-CSCs might transform into CSCs and thus eradication of CSCs alone may not obtain complete regression of an established tumor. 5 Interestingly, our study indicated that HNF4 could induce the differentiation of both hepatoma cells and its CSCs. The suppression of CSCs was accompanied by the inhibition of a cluster of genes which contribute to the pluripotency of human stem cells, including-catenin, Oct3/4, SMO(smoothened homolog), Bmi, Sox2, NANOG, c-Myc, Klf4, LIN28, and ESG1 (enhancer of split groucho 1). 3 More recently, we also demonstrated that up-regulation of HNF4 remarkably ameliorated hepatic fibrosis 6 and prevented the development of HCC in rats accompanied by the revision of epithelial-mesenchymal transition (unpublished data). Thus, we believe that differentiation therapy with HNF4, a central regulator for hepatocyte differentiation, might be an ideal strategy for the treatment of human HCC. Moreover, this strategy may be extended to other cancer types through the induction of differentiation using their corresponding key transcription factors.

Rabies virus (RABV) is known to cause a fatal infection in many mammalian species, yet its pathogenesis remains poorly understood. This study was performed to analyze the microRNA (miRNA) expression profiles in RABV-infected primary neurons of mice. A total of 53 miRNAs were found to be differentially expressed in RABV-infected samples compared with mock samples in a time-dependent manner. Among them, the expression of ten miRNAs was validated by real-time RT-PCR. Potential target genes of differentially expressed miRNAs were predicted by TargetScan. Further bioinformatics analysis indicated that these predicted targets were overrepresented in neuronal function-related Gene Ontology (GO) terms and biological pathways. The results of this study suggest that RABV may cause neuronal dysfunction by regulating cellular miRNA expression.

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