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.
Highlights
MicroRNAs are important regulators for cancer cell proliferation. miR-585 has been shown to inhibit the proliferation of several types of cancer, little is known about its role in human glioma cells
We report an anti-proliferative function of miR-585 in human glioma cells, where the targeted murine double minute 2 (MDM2) constitutes a critical mechanism
Results miR‐585 expression is downregulated in human glioma tissues and cell lines To seek whether miR-585 is functionally involved in glioma pathogenesis, we firstly compared its expression levels between surrounding normal brain tissues and paired human glioma tissues by the quantitative real-time PCR analysis
Summary
MicroRNAs (miRNAs) are important regulators for cancer cell proliferation. miR-585 has been shown to inhibit the proliferation of several types of cancer, little is known about its role in human glioma cells. MicroRNAs (miRNAs) are important regulators for cancer cell proliferation. MiR-585 has been shown to inhibit the proliferation of several types of cancer, little is known about its role in human glioma cells. To identify novel therapeutic targets and develop more effective strategies for treating malignant gliomas, it is imperative to gain a better understanding of the molecular mechanisms that underlie glioma progression. Through regulating the expression of target genes, microRNAs (miRNAs), a class of small non-coding RNAs, play important roles in various cellular processes, such as proliferation, differentiation, apoptosis and migration [6]. Accumulating evidence has shown that the deregulation of several miRNAs is involved in the tumorigenesis and development of a broad range of cancers [7], including gliomas [8, 9].
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