This study was performed to determine whether
EMAP II increases the permeability of the blood-
tumor barrier (BTB) by affecting the expression of miR-330-3p as well as its possible mechanisms. We determined the over-expression of miR-330-3p in
glioma microvascular endothelial cells (GECs) by Real-time PCR.
Endothelial monocyte-activating polypeptide-II (
EMAP-II) significantly decreased the expression of miR-330-3p in GECs. Pre-miR-330-3p markedly decreased the permeability of BTB and increased the expression of tight junction (TJ) related
proteins ZO-1,
occludin and
claudin-5, however, anti-miR-330-3p had the opposite effects. Anti-miR-330-3p could enhance the effect of
EMAP-II on increasing the permeability of BTB, however, pre-miR-330-3p partly reversed the effect of
EMAP-II on that. Similarly, anti-miR-330-3p improved the effects of
EMAP-II on increasing the expression levels of PKC-α and p-PKC-α in GECs and pre-miR-330-3p partly reversed the effects. MiR-330-3p could target bind to the
3'UTR of PKC-α. The results of in vivo experiments were similar to those of in vitro experiments. These suggested that
EMAP-II could increase the permeability of BTB through inhibiting miR-330-3p which target negative regulation of PKC-α. Pre-miR-330-3p and PKC-α inhibitor decreased the BTB permeability and up-regulated the expression levels of ZO-1,
occludin and
claudin-5 while anti-miR-330-3p and PKC-α activator brought the reverse effects. Compared with
EMAP-II, anti-miR-330-3p and PKC-α activator alone, the combination of the three combinations significantly increased the BTB permeability.
EMAP-II combined with anti-miR-330-3p and PKCα activator could enhance the DOX's effects on inhibiting the cell viabilities and increasing the apoptosis of U87
glioma cells. Our studies suggest that low-dose
EMAP-II up-regulates the expression of PKC-α and increases the activity of PKC-α by inhibiting the expression of miR-330-3p, reduces the expression of ZO-1,
occludin and
claudin-5, and thereby increasing the permeability of BTB. The results can provide a new strategy for the comprehensive treatment of
glioma.