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长链非编码RNA SNHG16通过海绵化miR-4518和上调PRMT5表达在胶质瘤中发挥癌基因作用。

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma.

作者信息

Lu Ye-Fen, Cai Xue-Li, Li Zheng-Zheng, Lv Jing, Xiang Yi-An, Chen Jian-Jun, Chen Wei-Jing, Sun Wei-Yan, Liu Xiu-Mei, Chen Jian-Bo

机构信息

Department of Neurology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China.

Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Cell Physiol Biochem. 2018;45(5):1975-1985. doi: 10.1159/000487974. Epub 2018 Mar 6.

Abstract

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma.

METHODS

The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed. The levels of proteins were detected using western blot. Bioinformatics analysis and luciferase reporter assays were applied to the analysis of the relationship between SNHG16, miR-4518 and PRMT5. Cell viability and apoptosis were measured using MTT and apoptosis ELISA assay, respectively.

RESULTS

SNHG16 was highly expressed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. Knockdown of SNHG16 inhibits the viability and induces apoptosis of glioma cells. Further investigation revealed that SNHG16 could up-regulate the expression of miR-4518 targeted gene PRMT5 via acting as an endogenous sponge of miR-4518. Moreover, SNHG16 also affects the expression of Bcl-2 family proteins and the activation of PI3K/Akt signaling pathway.

CONCLUSION

Our study revealed a novel SNHG16-miR-4518-PRMT5 pathway regulatory axis in glioma pathogenesis. SNHG16 could be used as a potential therapeutic target in the treatment of glioma.

摘要

背景/目的:长链非编码RNA(lncRNAs)最近已成为各种癌症中新型且具有潜在前景的治疗靶点。然而,lncRNAs在胶质瘤中的表达模式和生物学功能仍 largely难以捉摸。在本研究中,我们调查了一种lncRNA,小核仁RNA宿主基因16(SNHG16)在胶质瘤中的功能作用。

方法

使用qRT-PCR测量SNHG16和miR-4518的表达水平。对SNHG16水平与临床病理特征之间的关系进行统计学分析。使用蛋白质印迹法检测蛋白质水平。应用生物信息学分析和荧光素酶报告基因测定法分析SNHG16、miR-4518和PRMT5之间的关系。分别使用MTT和凋亡ELISA测定法测量细胞活力和凋亡。

结果

SNHG16在胶质瘤组织和细胞系中高表达,这与较差的临床病理特征和较短的生存时间相关。敲低SNHG16可抑制胶质瘤细胞的活力并诱导其凋亡。进一步研究表明,SNHG16可通过作为miR-4518的内源性海绵上调miR-4518靶向基因PRMT5的表达。此外,SNHG16还影响Bcl-2家族蛋白的表达和PI3K/Akt信号通路的激活。

结论

我们的研究揭示了胶质瘤发病机制中一种新的SNHG16-miR-4518-PRMT5途径调控轴。SNHG16可作为胶质瘤治疗的潜在治疗靶点。

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