MicroRNA-585 inhibits human glioma cell proliferation by directly targeting MDM2
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PRIMARY RESEARCH
Cancer Cell International Open Access
MicroRNA‑585 inhibits human glioma cell proliferation by directly targeting MDM2 Wangsheng Chen1, Lan Hong2, Changlong Hou3, Yibin Wang3, Fei Wang1 and Jianhua Zhang3*
Abstract Background: MicroRNAs (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. Methods: miR-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). Results: miR-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. Conclusions: Our study unveils the anti-proliferative role of miR-585 in human glioma cells, and also implicates its potential application in clinical therapy. Keywords: MicroRNA-585, Human glioma cell, Proliferation, MDM2, MRI Background Malignant gliomas are the most common type of brain tumors characterized by aggressive progression and chemoresistance, causing extremely poor clinical prognosis and high mortality [1–3]. Although rapid progress has been obtained in diagnostic methods and therapies in recent decades, the prognosis of malignant gliomas has not been significantly improved, and many patients succumb to the disease within 5 years after diagnosis [4, 5]. *Correspondence: [email protected] 3 Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, No 150, JiMo Road, Pudong New Area, Shanghai 200120, China Full list of author information is available at the end of the article
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]. Recen
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