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Regulation of MMP-2 expression and activity by β-1,3-N-acetylglucosaminyltransferase-8 in AGS gastric cancer cells

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Abstract

β-1,3-N-acetylglucosaminyltransferase-8(β3Gn-T8) catalyzes the transfer of GlcNAc to the non-reducing terminus of the Galβ1-4GlcNAc of tetraantennary N-glycan in vitro. It has been reported to be involved in malignant tumors, but a comprehensive understanding of how the glycolsyltransferase correlates with the invasive potential of human gastric cancer is not currently available. Therefore, we investigated the ability and possible mechanism involved with β3Gn-T8 in modulating matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in AGS gastric cancer cells. Here, we found out that siRNA-mediated suppression of the β3Gn-T8 could directly reduce the MMP-2 expression and activity as observed in RT-PCR, western blot and gelatin zymography analysis. Meanwhile, TIMP-2 expression had been increased. Cell invasion assay using matrigel matrix-coated transwell inserts showed that the invasive property was greatly suppressed in β3Gn-T8 siRNA transfected cells. Furthermore, cells overexpressing β3Gn-T8 gene (when transfected with pEGFP-C1 plasmid) also expressed MMP-2 gene, but TIMP-2 expression had been inhibited. The invasive ability of these cells was also enhanced. Protein–protein interaction analysis using STRING database showed that β3Gn-T8 and MMP-2 may have related signal pathway. In summary, our results reveal a new mechanism by which β3Gn-T8 can regulate MMP-2 and TIMP-2. We suggest that β3Gn-T8 can be used as a novel therapeutic target for human gastric treatment.

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Acknowledgment

This work was supported by grants from National Natural Science Foundation of China to Q.C. (No. 30670462).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Soochow University, Suzhou, 215123, Jiangsu, China

    Li Shen, Lan Xu & Shiliang Wu

  2. Department of Inspection, Suzhou Health College, Suzhou, 215001, Jiangsu, China

    Zhenhua Liu & Xiaoya Sun

  3. Department of Bioinformatics, Soochow University, Suzhou, 215123, Jiangsu, China

    Youbin Tu

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  1. Li Shen
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  2. Zhenhua Liu
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  3. Youbin Tu
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Correspondence to Shiliang Wu.

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Shen, L., Liu, Z., Tu, Y. et al. Regulation of MMP-2 expression and activity by β-1,3-N-acetylglucosaminyltransferase-8 in AGS gastric cancer cells. Mol Biol Rep 38, 1541–1550 (2011). https://doi.org/10.1007/s11033-010-0262-4

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