miR-29c contribute to glioma cells temozolomide sensitivity by targeting O(6)-methylguanine-DNA methyltransferases indirectly

Temozolomide (TMZ) is the most commonly used alkylating agent in glioma chemotherapy. However growing resistance to TMZ remains a major challenge to clinicians. The DNA repair protein O(6)-methylguanine-DNA methytransferase (MGMT) plays critical roles in TMZ resistance. Promoter methylation can inhibit MGMT expression and increase chemosensitivity. Here, we described a novel mechanism regulating MGMT expression. We showed that miR-29c suppressed MGMT expression indirectly via targeting specificity protein 1 (Sp1). MiR-29c overexpression increased TMZ efficacy in cultured glioma cells and in mouse xenograft models. The miR-29c levels were positively correlated with patient outcomes. Our data suggest miR-29c may be potential therapeutic targets for glioma treatment.