MiR-107Induces Cell Apotosis In Glioma By Downregulation Of SALL4

Glioma is the most common highly malignant primary brain tumor. Nowdays themolecular pathways in the pathogenesis of glioma remain elusive. In order to clarify thesignal pathway, we showed that miR-107knockdown promoted cell growth in MO59Kby MTT analysis. FADD was increased in miR-107overexpressied glioma cell linesSHG44, U251and U87，and so was the activity of caspases8. Moreover, the activity ofcaspase8in miR-107-overexpressing SHG44cells was suppressed with FADDknockdown by rescue experiments, which suggest upregulation of miR-107suppressedglioma cell growth and induced apoptosis through the increase of FADD expression.To verify the downstream target molecules of miR-107, we usedImmunofluorescence,and the results indicated that SALL4expression wasdown-regulated in SHG44cells after miR-107overexpression，and SALL4expressionwas up-regulated in MO59K cells after miR-107knockdown.SALL43′-UTR-dependentluciferase activity was reduced by miR-107mimics in SHG44, U251and U87cells andwas increased in MO59K cells. These results show that the5′seed sequence of miR-107is important site to bind with SALL4.To investigate the function of oncogene SALL4, RNA interference experimentswere performed. SALL4downregulation triggered growth inhibition. Using Annexin Vand PI double staining method, qRT-PCR, western blot and caspase8, caspase3/7activity assay, we show that SALL4induced cell apoptosis and suppressed glioma cellgrowth through FADD upregulation. To clarify the role of SALL4in miR-107-inducedapoptosis, the rescue experiments were performed by SALL4overexpression. The resultshowed that the caspase-8activity in miR-107-overexpressing SHG44cells wassuppressed with SALL4upregulation, which suggests miR-107induces cell apoptosisby inhibiting the expression of SALL4.In summary, our results demonstrate upregulation of miR-107suppressed gliomacell growth through direct targeting of SALL4, leading to the activation ofFADD/caspase-8/caspase-3/7signaling pathway of cell apoptosis. These data suggestmiR-107is a potential therapeutic target against glioma.