期刊
ONCOTARGET
卷 7, 期 31, 页码 50229-50238出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10357
关键词
glioblastoma; TMZ; MGMT; miR-29c; chemoresistance
资金
- National Natural Science Foundation of China [30901539, 31270992]
- Ministry of Science and Technology of China [2014BAI04B02]
- Science and Technology Planning Project of Guangdong Province [2011B031800138, 2013B021800275]
- project of Zhu Jiang Science and Technology new star of Guangzhou City [2013J2200019]
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.
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