microRNA-22 downregulation of galectin-9 influences lymphocyte apoptosis and tumor cell proliferation in liver cancer.

Abstract Galectin-9 (Gal-9) 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.