EZH2 alteration driven by microRNA-524-5p and microRNA-324-5p promotes cell proliferation and temozolomide resistance in glioma
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Tongle Zhi1,*, Tianfu Yu1,*, Minhong Pan2,*, Er Nie1, Weining Wu1, Xiefeng Wang1, Ning Liu1, Yongping You1, Yingyi Wang1 and Junxia Zhang1
1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
2Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
*These authors have contributed equally to this work
Yingyi Wang, email: email@example.com
Junxia Zhang, email: firstname.lastname@example.org
Keywords: EZH2; miRNA; prognosis; TMZ; glioma
Received: June 28, 2017 Accepted: August 27, 2017 Published: October 24, 2017
Recent data have been shown that EZH2 is a critical oncogene via the repression of tumor suppressor genes in human cancers. In our study, we performed a genome-wide miRNA screen with a bioinformatics analysis to identify EZH2 specific miRNAs. Of these miRNAs, miR-524-5p and miR-324-5p were decreased in glioma tissues, and confered poor prognosis for glioma patients. Upregulation of miR-524-5p and miR-324-5p reduced glioma cell proliferation and increased temozolomide (TMZ) chemosensitivity by targeting EZH2. Importantly, the effection of miR-524-5p and miR-324-5p on cell proliferation and TMZ chemosensitivity in glioma were reversed by expression of EZH2 cDNA. Further, miR-524-5p and miR-324-5p overexpression suppressed glioma growth and prolonged survival in an intracranial xenograft model. Multivariate Cox regression analysis revealed that miR-524-5p was an independent prognostic factor in gliobalstoma patients. Taken together, these data indicate that miRNA-driven EZH2 repression may provide evidence of the molecular mechanism for gliomagenesis and the novel therapeutic targets for glioma.
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