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mir-218-2通过靶向细胞分裂周期蛋白27(CDC27)促进胶质母细胞瘤的生长、侵袭和耐药性。

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

作者信息

Feng Zhuoying, Zhang Luping, Zhou Junchen, Zhou Shuai, Li Li, Guo Xuyan, Feng Guoying, Ma Ze, Huang Wenhua, Huang Fei

机构信息

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.

出版信息

Oncotarget. 2017 Jan 24;8(4):6304-6318. doi: 10.18632/oncotarget.13850.

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8675/5351633/78d3b67c70d7/oncotarget-08-6304-g001.jpg

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