miR-29c contribute to glioma cells temozolomide sensitivity by targeting O6-methylguanine-DNA methyltransferases indirectly
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Songhua Xiao1,*, Zhen Yang2,*, Xingsheng Qiu3,*, Ruiyan Lv1, Jun Liu1, Ming Wu4, Yiwei Liao4, Qing Liu4
1Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guanzhou, Guangdong, China
2Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
3Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
4Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
*These authors have contributed equally to this work
Qing Liu, email: firstname.lastname@example.org
Keywords: glioblastoma, TMZ, MGMT, miR-29c, chemoresistance
Received: November 28, 2015 Accepted: May 28, 2016 Published: July 1, 2016
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 O6-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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