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miR-29c contribute to glioma cells temozolomide sensitivity by targeting O6-methylguanine-DNA methyltransferases indirectly

2016; Impact Journals LLC; Volume: 7; Issue: 31 Linguagem: Inglês

10.18632/oncotarget.10357

1949-2553

Songhua Xiao, Zhen Yang, Xingsheng Qiu, Ruiyan Lv, Jun Liu, Ming Wu, Yiwei Liao, Qing Liu,

Epigenetics and DNA Methylation

// Songhua Xiao 1, * , Zhen Yang 2, * , Xingsheng Qiu 3, * , Ruiyan Lv 1 , Jun Liu 1 , Ming Wu 4 , Yiwei Liao 4 , Qing Liu 4 1 Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guanzhou, Guangdong, China 2 Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China 3 Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China 4 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China * These authors have contributed equally to this work Correspondence to: Qing Liu, email: chingliucn@yahoo.com Keywords: glioblastoma, TMZ, MGMT, miR-29c, chemoresistance Received: November 28, 2015 Accepted: May 28, 2016 Published: July 1, 2016 ABSTRACT 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.