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微小RNA-10b通过靶向AKT降低胶质母细胞瘤细胞对辐射的敏感性。

MiR-10b decreases sensitivity of glioblastoma cells to radiation by targeting AKT.

作者信息

Zhen Limin, Li Jian, Zhang Mingran, Yang Kun

机构信息

Department of Neurosurgery, Taian Central Hospital, No. 29, Longtan Road, Taian City, Shandong Province China.

出版信息

J Biol Res (Thessalon). 2016 Jun 24;23:14. doi: 10.1186/s40709-016-0051-x. eCollection 2016 Dec.

Abstract

BACKGROUND

Glioblastomas are the most aggressive brain tumors with extremely poor prognosis despite advances in treatment techniques. MiR-10b is highly expressed in glioblastoma and regulates cell proliferation, migration and invasion. Here, we examined the role of MiR-10b on radiotherapy of glioblastomas.

METHODS

MiR-10b mimic or anti-MiR-10b inhibitor was transfected in glioblastoma cells. WST-1 assay was used to examine the effect of MiR-10b on proliferation of transfected glioblastoma cells after radiation treatment. Apoptosis was examined by caspase 3/7 activity and TUNEL assay. The western blot was used to evaluate protein expression.

RESULTS

Altered expression of MiR-10b changed the radiation-induced inhibitory effect on proliferation of glioblastoma cells with dose-dependent manner. MiR-10b decreased radiation-induced apoptosis in glioblastoma cells by activation of caspase 3/7 and inhibition Bcl-2 expression. MiR-10b enhances migration and invasion of glioblastoma cells in presence of radiation. In addition, MiR-10b decreased the sensitivity of glioblastoma cells to radiotherapy by activation of p-AKT expression.

CONCLUSIONS

MiR-10b might be a potential biomarker to predict radiotherapy response and prognosis in glioblastomas.

摘要

背景

胶质母细胞瘤是最具侵袭性的脑肿瘤,尽管治疗技术有所进步,但其预后极差。MiR-10b在胶质母细胞瘤中高表达,并调节细胞增殖、迁移和侵袭。在此,我们研究了MiR-10b在胶质母细胞瘤放射治疗中的作用。

方法

将MiR-10b模拟物或抗MiR-10b抑制剂转染到胶质母细胞瘤细胞中。采用WST-1法检测MiR-10b对放射治疗后转染的胶质母细胞瘤细胞增殖的影响。通过caspase 3/7活性和TUNEL检测来检测细胞凋亡。使用蛋白质印迹法评估蛋白质表达。

结果

MiR-10b表达的改变以剂量依赖的方式改变了辐射诱导的对胶质母细胞瘤细胞增殖的抑制作用。MiR-10b通过激活caspase 3/7和抑制Bcl-2表达降低了辐射诱导的胶质母细胞瘤细胞凋亡。在有辐射的情况下,MiR-10b增强了胶质母细胞瘤细胞的迁移和侵袭。此外,MiR-10b通过激活p-AKT表达降低了胶质母细胞瘤细胞对放射治疗的敏感性。

结论

MiR-10b可能是预测胶质母细胞瘤放射治疗反应和预后的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5138/4921021/5e36f8bb4592/40709_2016_51_Fig1_HTML.jpg

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