Glioma is recognized as a highly angiogenic malignant brain tumor. Vasculogenic 
mimicry (VM) greatly restricts the therapeutic effect of anti-angiogenic tumor 
therapy for glioma patients. However, the molecular mechanisms of VM formation 
in glioma remain unclear. Here, we demonstrated that LINC00339 was upregulated 
in glioma tissue as well as in glioma cell lines. The expression of LINC00339 in 
glioma tissues was positively correlated with glioma VM formation. Knockdown of 
LINC00339 inhibited glioma cell proliferation, migration, invasion, and tube 
formation, meanwhile downregulating the expression of VM-related molecular MMP-2 
and MMP-14. Furthermore, knockdown of LINC00339 significantly increased the 
expression of miR-539-5p. Both bioinformatics and luciferase reporter assay 
revealed that LINC00339 regulated the above effects via binding to miR-539-5p. 
Besides, overexpression of miR-539-5p resulted in decreased expression of 
TWIST1, a transcription factor known to play an oncogenic role in glioma and 
identified as a direct target of miR-539-5p. TWIST1 upregulated the promoter 
activities of MMP-2 and MMP-14. The in vivo study showed that nude mice carrying 
tumors with knockdown of LINC00339 and overexpression of miR-539-5p exhibited 
the smallest tumor volume through inhibiting VM formation. In conclusion, 
LINC00339 may be used as a novel therapeutic target for VM formation in glioma.