Feng Zhuoying, Zhang Luping, Zhou Junchen, Zhou Shuai, Li Li, Guo Xuyan, Feng Guoying, Ma Ze, Huang Wenhua, Huang Fei
Institute of Human Anatomy and Histology and Embryology, Otology & Neuroscience Center, Binzhou Medical University, Laishan District, Shandong Province, 264003,China.
Institute of Clinical Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Oncotarget. 2017 Jan 24;8(4):6304-6318. doi: 10.18632/oncotarget.13850.
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.
神经胶质瘤已成为一个严重的全球健康问题,具有很高的发病率和死亡率,这凸显了阐明其潜在分子机制的重要性。最近的研究已将mir-218鉴定为一种抗癌基因;然而,mir-218-1和mir-218-2的具体功能仍然未知,尤其是后者。本研究的目的是进一步探究mir-218-2在神经胶质瘤中的作用。我们的结果表明,mir-218-2在神经胶质瘤中高度过表达。此外,我们发现mir-218-2与神经胶质瘤细胞的生长、侵袭、迁移及药物敏感性(对β-拉帕醌)呈正相关。在体外,mir-218-2的过表达促进了神经胶质瘤细胞的增殖、侵袭和迁移。另外,在体内发现mir-218-2的过表达会增加神经胶质瘤肿瘤的生长。相应地,抑制mir-218-2则产生相反的效果。细胞分裂周期27(CDC27)是mir-218-2的下游靶点,参与神经胶质瘤细胞的调控。我们的结果表明,CDC27的过表达抵消了mir-218-2在神经胶质瘤细胞中的功能。这些新发现为将mir-218-2作为一种潜在的神经胶质瘤治疗方法的应用提供了新的见解。