Our study showed that piR-DQ590027 can decrease the expression of ZO-1, claudin-5, and occludin and increase the permeability of glioma-conditioned normal BBB, suggesting that piR-DQ590027 overexpression increases the permeability of glioma-conditioned normal BBB via the paracellular pathway. Here, CLDN5 is linked to central nervous system cancer.