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miR-32 通过靶向 EZH2 抑制神经胶质瘤的增殖和转移。

MiR-32 Inhibits Proliferation and Metastasis by Targeting EZH2 in Glioma.

机构信息

1 Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan City, Shandong Province, People's Republic of China.

2 Shandong Key Laboratory of Brain Function Remodeling, Jinan City, Shandong Province, People's Republic of China.

出版信息

Technol Cancer Res Treat. 2019 Jan-Dec;18:1533033819854132. doi: 10.1177/1533033819854132.

Abstract

PURPOSE

Glioma is identified as a broad category of brain and spinal cord tumors. MiR-32 is important in regulating the genesis of different cancers; however, the underlying mechanisms of miR-32 in glioma still largely unknown. This study aimed to elucidate pathobiological functions of miR-32 in glioma and verify its effect on the regulation of enhancer of zeste homolog 2.

METHODS

The expression of miR-32 and enhancer of zeste homolog 2 was detected by quantitative real-time polymerase chain reaction and Western blot in glioma tissues and cells. Cell Counting Kit-8 (CCK-8) assay was used to examine the effects of miR-32 on human glioma cells proliferation. Transwell assay was used to examine cell metastasis, respectively. Two bioinformatics analysis software and luciferase reporter assay were chosen to confirm targeting association between miR-32 and enhancer of zeste homolog 2.

RESULTS

MiR-32 was downregulated in glioma tissues and cells. Furthermore, enhancer of zeste homolog 2 expression was upregulated and negatively correlated with miR-32 in clinical tissues. Ectopic expression of miR-32 inhibited glioma cell proliferation, migration, and invasion. Enhancer of zeste homolog 2 was identified as direct target gene of miR-32 in glioma. Overexpression of enhancer of zeste homolog 2 ablated the inhibitory effects of miR-32.

CONCLUSION

In summary, our finding suggests that miR-32 acts an important role in inhibiting glioma cell proliferation and metastasis and suppresses the expression of ABCC4 by directly targeting its 3'-untranslated region. The miR-32/enhancer of zeste homolog 2 axis may provide new insights to the treatment for glioma.

摘要

目的

神经胶质瘤被鉴定为广泛的脑和脊髓肿瘤类别。miR-32 在调节不同癌症的发生中起着重要作用;然而,miR-32 在神经胶质瘤中的潜在机制在很大程度上仍然未知。本研究旨在阐明 miR-32 在神经胶质瘤中的病理生物学功能,并验证其对增强子的调节作用Zeste 同源物 2。

方法

通过定量实时聚合酶链反应和 Western blot 检测 miR-32 和增强子在神经胶质瘤组织和细胞中的表达Zeste 同源物 2。细胞计数试剂盒-8(CCK-8)检测 miR-32 对人神经胶质瘤细胞增殖的影响。Transwell 检测分别用于细胞转移。选择两种生物信息学分析软件和荧光素酶报告基因检测来证实 miR-32 与增强子之间的靶向关联Zeste 同源物 2。

结果

miR-32 在神经胶质瘤组织和细胞中下调。此外,增强子在临床组织中上调Zeste 同源物 2 表达与 miR-32 呈负相关。miR-32 的异位表达抑制神经胶质瘤细胞的增殖、迁移和侵袭。增强子被鉴定为 miR-32 在神经胶质瘤中的直接靶基因Zeste 同源物 2。过表达增强子Zeste 同源物 2 消除了 miR-32 的抑制作用。

结论

总之,我们的研究结果表明,miR-32 通过直接靶向其 3'-非翻译区,在抑制神经胶质瘤细胞增殖和转移方面发挥重要作用,并抑制 ABCC4 的表达。miR-32/enhancer of zeste homolog 2 轴可能为神经胶质瘤的治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8a3/6542126/917289614916/10.1177_1533033819854132-fig1.jpg

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