MicroRNA-9 enhances chemotherapy sensitivity of glioma to TMZ by suppressing TOPO II via the NF-κB signaling pathway.

ABSTRACT

Glioma is the most common primary tumor of the central nervous system (CNS) that develops chemotherapy resistance. The microRNA (miRNA) miR-9 is a tissue-specific miRNA of the CNS that may serve a key role in the modulation of chemotherapy sensitivity. The aim of the present study was to investigate the effect of miR-9 on glioma chemotherapy sensitivity by altering the expression of miR-9 in U251 glioma cells by viral transfection and subsequently treating with gradient concentrations of temozolomide (TMZ). Cell viability, apoptosis and the cell cycle were examined, and drug resistance genes were analyzed by western blotting. The role of nuclear factor κB (NF-κB) in this regulation was also examined. The results revealed that the susceptibility of glioma cells to TMZ was enhanced by miR-9 overexpression. When miR-9 and TMZ were applied together, the apoptotic rate and percentage of cells arrested at the G2/M stage were significantly higher compared with either treatment alone. Topoisomerase II expression was suppressed by miR-9 via the NF-κB signaling pathway, which may be responsible for the sensitization. The results of the present study suggested that miR-9 may be a potential target for glioma chemotherapy.