miR-525-5p Modulates Proliferation and Epithelial-Mesenchymal Transition of Glioma by Targeting Stat-1

Onco Targets Ther. 2020 Oct 7:13:9957-9966. doi: 10.2147/OTT.S257951. eCollection 2020.

Abstract

Background: Glioma is the most aggressive human brain tumor. Recent studies revealed that microRNAs play vital roles in glioma. However, the function of microRNA-525-5p (miR-525-5p) in glioma remains unclear.

Methods: qRT-PCR and Western blotting were used to evaluate mRNA and protein levels in glioma tissues and cells. Colony formation, CCK-8, and Edu assays evaluated the growth of glioma cells. Wound-healing, transwell, and 3D invasion assays examined the migration and invasion activities of glioma cells. Luciferase reporter assays assessed the regulatory relationship interaction between miR-525-5p and Stat-1. A mouse xenograft model was used to examine the effect of miR-525-5p on glioma in vivo.

Results: miR-525-5p expression was downregulated in glioma tissues and cells. Overexpressing miR-525-5p decreased the growth of glioma cells and reduced the migration, invasion, and epithelial-mesenchymal transition of glioma cells. Bioinformatics analysis identified Stat-1 as a potential target of miR-525-5p, and dual luciferase reporter assays revealed that miR-525-5p negatively regulates Stat-1. Decreased Stat-1 led to the inhibition of FOXM1, affecting NF-κB signaling activity. Overexpressing miR-525-5p reduced tumor development in vivo.

Conclusion: miR-525-5p negatively regulates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in glioma, and Stat 1 is a target of miR-525-5p. miR-525-5p may be a potential target for glioma treatment.

Keywords: EMT; Stat 1; glioma; miR-525-5p; proliferation.

Grants and funding

This study was supported by the Research Program of Science and Technology Support Program of Huai’an (HAB201931) and Open Project of Key Laboratory of Universities of Jiangsu Province (XZSYSKF2019002).