Low-expression of microRNA-107 inhibits cell apoptosis in glioma by upregulation of SALL4.

Glioma is the most common highly malignant primary brain tumor. The molecular pathways that result in the pathogenesis of glioma remain elusive. In this study, we found microRNA-107 (miR-107) was downregulated in glioma tissues and cell lines. Our results revealed miR-107 overexpression suppressed cell proliferation in glioma cells, whereas miR-107 knockdown promoted cell growth in MO59K. miR-107 expression induced apoptosis in glioma cells possibly through the increase in Fas (TNFRSF6)-associated via death domain (FADD) expression and activation of caspases-8 and -3/7. Moreover, the activity of caspase-8 in miR-107-overexpressing SHG44 cells was suppressed with FADD knockdown. The tumor growth in nude mice bearing miR-107-overexpressing SHG44 cells was blocked through apoptosis induction. Sal-like 4 (Drosophila) (SALL4) level was reduced upon miR-107 overexpression in glioma cells, and the inverse was observed upon miR-107 knockdown in MO59K. Using a luciferase reporter system, SALL4 3'-UTR-dependent luciferase activity was reduced by miR-107 mimics or increased by an inhibitor of miR-107. In SHG44, SALL4 downregulation triggered growth inhibition and activated FADD-mediated cell apoptosis pathway. The caspase-8 activity in miR-107-overexpressing SHG44 cells was suppressed with SALL4 upregulation. Furthermore, primary glioma tumors with low miR-107 expression show elevated SALL4 level. An obvious inverse correlation was observed between miR-107 expression and SALL4 level in clinical glioma samples. Therefore, our results demonstrate upregulation of miR-107 suppressed glioma cell growth through direct targeting of SALL4, leading to the activation of FADD/caspase-8/caspase-3/7 signaling pathway of cell apoptosis. These data suggest miR-107 is a potential therapeutic target against glioma.