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MicroRNA-585 inhibits human glioma cell proliferation by directly targeting MDM2

Authors
  • Chen, Wangsheng1
  • Hong, Lan1
  • Hou, Changlong2
  • Wang, Yibin2
  • Wang, Fei1
  • Zhang, Jianhua2
  • 1 Hainan General Hospital/Hainan Hospital of Hainan Medical University, Haikou, 570311, China , Haikou (China)
  • 2 Tongji University School of Medicine, No 150, JiMo Road, Pudong New Area, Shanghai, 200120, China , Shanghai (China)
Type
Published Article
Journal
Cancer Cell International
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Sep 29, 2020
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12935-020-01528-w
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundMicroRNAs (miRNAs) are important regulators for cancer cell proliferation. miR-585 has been shown to inhibit the proliferation of several types of cancer, however, little is known about its role in human glioma cells.MethodsmiR-585 levels in human glioma clinical samples and cell lines were examined by quantitative real-time PCR (qRT-PCR) analysis. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and EdU incorporation assays in vitro. For in vivo investigations, U251 cells were intracranially inoculated in BALB/c nude mice and xenografted tumors were visualized by magnetic resonance imaging (MRI).ResultsmiR-585 expression is downregulated in human glioma tissues and cell lines compared with non-cancerous counterparts. Additionally, miR-585 overexpression inhibits and its knockdown promotes human glioma cell proliferation in vitro. Moreover, miR-585 overexpression also inhibits the growth of glioma xenografts in vivo, suggesting that miR-585 may act as a tumor suppressor to inhibit the proliferation of human glioma. Furthermore, miR-585 directly targets and decreases the expression of oncoprotein murine double minute 2 (MDM2). More importantly, the restoration of MDM2 via enforced overexpression markedly rescues miR-585 inhibitory effect on human glioma cell proliferation, thus demonstrating that targeting MDM2 is a critical mechanism by which miR-585 inhibits human glioma cell proliferation.ConclusionsOur study unveils the anti-proliferative role of miR-585 in human glioma cells, and also implicates its potential application in clinical therapy.

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