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BackgroundRecent studies have shown that interferon-γ (IFN-γ)-induced galectin-9 expression in Kupffer cells plays an essential role in modulatingthe microenvironment of hepatitis-associated hepatocellular carcinoma (HCC). However, whether or not IFN-γ induces galectin-9 expression in HCC cells, its biological role and regulatory mechanism in HCC development and progression are poorly defined.MethodsQuantitative PCR and western blotting analysis were used to detect galectin-9 and EZH2 levels in HCC cell lines stimulated with IFN-γ. Bioinformatics analysis and luciferase reporter assay were utilized to confirmthe binding ofmiR-22 to the 3′ untranslated region (3’-UTR) of galectin-9. The methylation status of miR-22 promoter was analyzed by MSP (Methylation specific PCR) and BSP (bisulfite sequencing PCR), while chromatin immunoprecipitation (ChIP) assay identify the occupation status of EZH2 and H3K27me3 at the promoter. Furthermore, the effect of ectopic expression of galectin-9 and miR-22 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, transwell assays and flow cytometric analysis, respectively.ResultsIFN-γ induces up-regulation of galectin-9 and EZH2 in HCC cell lines. Galectin-9 is a target of miR-22 and EZH2 facilitates galectin-9 expression by tri-methylation of H3K27 on miR-22 promoter but not hyper-methylation status of DNA. MiR-22 overexpression suppressed HCC cell growth, invasion, and metastasis both in vitro and in vivo. Interestingly, galectin-9 also exhibited antitumor effects, and restoring galectin-9 expression in miR-22 overexpressing cells strengthened its antitumor effects.ConclusionsThese findings indicated that EZH2 facilitates galectin-9 expression by epigenetically repressing miR-22 and that galectin-9, which is known as an immunosuppressant, also functions as a tumor suppressor in HCC.Electronic supplementary materialThe online version of this article (10.1186/s13046-017-0670-6) contains supplementary material, which is available to authorized users.

Introducing Clifford algebra as the mathematical foundation, a unified spatiotemporal data model and hierarchical spatio-temporal index are constructed by linking basic data objects, like pointclouds and Spatio-Temporal Hyper Cubes of different dimensions, within the multivector structure of Clifford algebra. The transformation from geographic space into homogeneous and conformal space means that geometric, metric and many other kinds of operators of Clifford algebra can be implemented and we then design the shortest path, high-dimensional Voronoi and unified spatial-temporal process analyses with spacetime algebra. Tests with real world data suggest these traditional GIS analysis algorithms can be extended and constructed under Clifford Algebra framework, which can accommodate multiple dimensions. The prototype software system CAUSTA (Clifford Algebra based Unified Spatial-Temporal Analysis) provides a useful tool for investigating and modeling the distribution characteristics and dynamic process of complex geographical phenomena under the unified spatio-temporal structure.

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