mir-218-2 promotes glioblastomas growth, invasion and drug resistance by targeting CDC27

2017 
// Zhuoying Feng 1, * , Luping Zhang 1, * , Junchen Zhou 1 , Shuai Zhou 1 , Li li 1 , Xuyan Guo 1 , Guoying Feng 1 , Ze Ma 1 , Wenhua Huang 2 , Fei Huang 1 1 Institute of Human Anatomy and Histology and Embryology, Otology & Neuroscience Center, Binzhou Medical University, Laishan District, Shandong Province, 264003,China 2 Institute of Clinical Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China * These authors contributed to this work equally and should be considered as co-first authors Correspondence to: Fei Huang, email: hfei22518@163.com Wenhua Huang, email: huangwenhua2009@139.com Keywords: gliomas, mir-218-2, CDC27, proliferation, invasion Received: December 28, 2015     Accepted: November 02, 2016     Published: December 10, 2016 ABSTRACT Glioma has become a significant global health problem with substantial morbidity and mortality, underscoring the importance of elucidating its underlying molecular mechanisms. Recent studies have identified mir-218 as an anti-oncogene; however, the specific functions of mir-218-1 and mir-218-2 remain unknown, especially the latter. The objective of this study was to further investigate the role of mir-218-2 in glioma. Our results indicated that mir-218-2 is highly overexpressed in glioma. Furthermore, we showed that mir-218-2 is positively correlated with the growth, invasion, migration, and drug susceptibility (to β-lapachone) of glioma cells. In vitro , the overexpression of mir-218-2 promoted glioma cell proliferation, invasion, and migration. In addition, the overexpression of mir-218-2 in vivo was found to increase glioma tumor growth. Accordingly, the inhibition of mir-218-2 resulted in the opposite effects. Cell division cycle 27 (CDC27), the downstream target of mir-218-2, is involved in the regulation of glioma cells. Our results indicate that the overexpression of CDC27 counteracted the function of mir-218-2 in glioma cells. These novel findings provide new insight in the application of mir-218-2 as a potential glioma treatment.
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