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miRNA-448 通过调节 Rho 相关蛋白激酶 1 调节神经胶质瘤(GBM)的发展。

miRNA-448 Regulates the Development of Glioblastoma (GBM) by Regulating Rho-Associated Protein Kinase 1.

机构信息

Neurosurgery Department, Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao 028007, China.

出版信息

Comput Math Methods Med. 2022 Mar 3;2022:2502010. doi: 10.1155/2022/2502010. eCollection 2022.

Abstract

BACKGROUND

Glioblastoma (GBM) is an aggressive adult brain tumor that poses a huge threat to people's health. Previous studies have shown that microRNAs (miRNAs) are important regulators in the progression of GBM. However, the role of miR-448 in GBM remains largely unknown. Therefore, the regulatory mechanism of miR-448 in the development of GBM is elucidated in this study.

METHODS

The protein and mRNA expressions of miR-448 and ROCK1 were measured by Western blot analysis and RT-qPCR. Cell proliferation, migration, and invasion were detected by CCK-8 assay and Transwell assay. The relationship between miR-448 and ROCK1 was probed by luciferase reporter assay.

RESULTS

miR-448 expression was downregulated in GBM tissues and cells. And poor clinical outcomes of GBM patients were related to miR-448 downregulation. Functionally, overexpression of miR-448 restrained cell viability, migration, and invasion in GBM. Additionally, miR-448 reduced ROCK1 expression by binding to its 3'-UTR. Moreover, knockdown of ROCK1 inhibited the progression of GBM. Furthermore, overexpression of ROCK1 abolished the antitumor effect of miR-448 in GBM.

CONCLUSION

miR-448 restrained cell viability, invasion, and migration in GBM by inhibiting ROCK1 expression.

摘要

背景

胶质母细胞瘤(GBM)是一种侵袭性的成人脑肿瘤,对人们的健康构成了巨大威胁。先前的研究表明 microRNAs(miRNAs)是 GBM 进展中的重要调节因子。然而,miR-448 在 GBM 中的作用在很大程度上仍然未知。因此,本研究阐明了 miR-448 在 GBM 发育中的调节机制。

方法

通过 Western blot 分析和 RT-qPCR 测量 miR-448 和 ROCK1 的蛋白和 mRNA 表达。通过 CCK-8 测定和 Transwell 测定检测细胞增殖、迁移和侵袭。通过荧光素酶报告基因测定探测 miR-448 和 ROCK1 之间的关系。

结果

miR-448 在 GBM 组织和细胞中表达下调。GBM 患者的不良临床结局与 miR-448 下调有关。功能上,miR-448 的过表达抑制了 GBM 中的细胞活力、迁移和侵袭。此外,miR-448 通过结合其 3'-UTR 降低 ROCK1 表达。此外,ROCK1 的敲低抑制了 GBM 的进展。此外,ROCK1 的过表达消除了 miR-448 在 GBM 中的抗肿瘤作用。

结论

miR-448 通过抑制 ROCK1 的表达来抑制 GBM 中的细胞活力、侵袭和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae19/8913139/11d6cc64ff71/CMMM2022-2502010.001.jpg

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