Abstract. plays an important role in both the immune response and tumor progression, while microRNAs act as tumor regulators to mediate tumorigenesis. However, the underlying molecular mechanisms remain unknown. In the present study, we investigated the relationship between Gal-9 and microRNA-mediated regulation in liver cancer. We examined Gal-9 expression using qRT-PCR and western blot analysis and found that it was markedly upregulated in human liver cancer cells compared with the level in normal hepatocytes. We co-cultured peripheral blood mononuclear cells (PBMCs) and tumor cells and observed that Gal-9 induced lymphocyte apoptosis and tumor cell immune escape using flow cytometric analysis and WST-1 assay. We found that miR-22 was downregulated in liver cancer tissues and cell lines and confirmed that miR-22 directly targeted the Gal-9 3'UTR and negatively regulated Gal-9 expression by luciferase reporter assay and transfection of microRNA mimics. We also observed that the Gal-9/miR-22 axis may influence lymphocyte apoptosis and tumor cell proliferation. These studies contribute to a further understanding of the microRNA-mediated regulation of the Gal-9 pathway and elucidate novel therapeutic targets for liver cancer.

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Abstract.Although there is evidence that galectin-9 is a critical factor in health and disease, the upstream regulatory microRNA (miRNA or miR) of the protein remains poorly defined. miR-455-5p is characterized as a tumor-associated miRNA in cancer research. However, the actual role of miR-455-5p with respect to inhibiting or promoting tumorigenesis in colon cancer is unclear. The present study aimed to investigate the expression, role and target regulation association of galectin-9 and miR-455-5p in colon cancer. Western blot analysis and reverse transcription-quantitative polymerase chain reaction were used for the detection of the expression levels of galectin-9 and miRNAs. Cell Counting kit-8 test was used for the evaluation of cell proliferation, while flow cytometry was used for cell apoptosis analysis. A potential interaction between galectin-9 and miR-455-5p was predicted by target prediction programs and confirmed by luciferase assay and transfection with miRNA mimics. The present study revealed that elevated expression of galectin-9 and miR-455-5p in colon cancer was associated with HT29 cell proliferation and apoptosis. Furthermore, the present study demonstrated that miR-455-5p reduced galectin-9 expression by directly targeting its 3'-untranslated region. These data suggest that miR-455-5p functions as a potential oncogene in colon cancer by targeting galectin-9.