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Aim Aberrant expression of Snail, a mediator of epithelial-mesenchymal transition (EMT), is crucial for cancer invasiveness and metastasis. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, the relationship between HCV core and Snail expression has not been clarified. Methods HepG2 and Huh7 stable cell lines were established by transfection with pcDNA-HCVc. HepG2-HCVc and Huh7-HCVc cells were co-administered with AG490. Cell migration and invasiveness were tested. STAT3 and Snail expression was analyzed by Real-time PCR and Western blot. Results We found that HCV core is capable of increasing Snail expression and inducing EMT in hepatoma cells. HCV core-induced Snail expression was accompanied by activation of signal transducer and activator of transcription 3 (STAT3), inhibition of STAT3 abrogated HCV core-induced Snail expression and EMT. Furthermore, chromatin immunoprecipitation showed that phosphorylated STAT3 directly binds to the Snail promoter. Conclusion Collectively, these results suggest that HCV core would play a role in hepatocellular carcinoma invasiveness and metastasis by activating the STAT3 pathway, increasing Snail expression and subsequently triggering EMT. These findings would advance the understanding of HCV-mediated invasiveness and metastasis, and might provide a new potential therapeutic target for HCV-related hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

o-Tetramethyl-substituted cucurbituril ( o-TMeQ[6]), a polydentate ligand, has been synthesized and isolated in a controlled manner by using a dimer of dimethyl-substituted glycoluril and a dimer of unsubstituted glycoluril. Coordination assemblies have been investigated by reactions between alkaline earth cations and o-TMeQ[6] in the presence of [CdCl4]2-, a structure inducer, in HCl aqueous solution. X-ray diffraction analysis revealed that o-TMeQ[6] coordinates with Ca2+ or Sr2+ and forms centrosymmetric tetranuclear assemblies in the presence of [CdCl4]2-. [CdCl4]2- typically produces the 'honeycomb effect' by forming honeycomb-like frameworks, which assist metal ions in coordinating to o-TMeQ[6]. The driving forces of this effect are the 'outer-surface interactions' of cucurbit[ n]urils. [ABSTRACT FROM AUTHOR]

Highlights: [•] A positive link between HCV Core expression, stat3 activation, and NANOG transcription is demonstrated. [•] HCV Core is capable of up-regulating NANOG expression in a STAT3 dependent manner. [•] Phosphorylated stat3 protein directly binds to the promoter of NANOG. [•] NANOG promotes cell growth and cell proliferation via NANOG/cyclin D1 pathway. [ABSTRACT FROM AUTHOR]

Background & Aims microRNA-122 is the only identified liver-specific miRNA and plays a crucial role in liver development, maintenance of hepatic homeostasis as well as tumourigenesis. In our previous differentiation of ESCs into hepatocytes, microRNA-122 (miR-122) was expressed at a relatively low level. Here, we aim to elucidate the effect and underlying mechanisms of miR-122 during differentiation of ESCs into hepatocytes. Methods Mouse ESCs were initially induced towards HPCs by activin A, FGF-4 and sodium butyrate and were subsequently transfected with a recombinant adenovirus expressing vector pAV.Ex1d-CMV>miR-122/IRES/eGFP 9 days after induction. Cells were analysed by real-time PCR, immunofluorescence, flow cytometry, microscopy and functional assays. Furthermore, microarray analysis was performed. Results We demonstrated that overexpression of miR-122 could effectively promote hepatic differentiation and maturation, as assessed by morphological and functional tests. The microarray analysis revealed that 323 genes were down-regulated, whereas 59 were up-regulated. Particularly, two liver-specific transcription factors, FoxA1 and HNF4a, were significantly up-regulated. Moreover, the expression of E-cadherin was dramatically increased and the proliferation of HPCs was suppressed, whereas knockdown of FoxA1 reduced E-cadherin expression and increased the proliferation of HPCs. In addition, the expression levels of FoxA1, HNF4a and E-cadherin in time-course transfection experiments with miR-122 were not significantly increased except in cells in which transfection with miR-122 occurred 9 days after induction. Conclusion Overexpression of miR-122 at an appropriate stage could promote hepatic differentiation and maturation by regulating the balance between proliferation and differentiation, as well as the balance between EMT and MET, partially through a miR-122/FoxA1/HNF4a-positive feedback loop. [ABSTRACT FROM AUTHOR]