<i>miR-218</i>
            opposes a critical RTK-HIF pathway in mesenchymal glioblastoma

Mathew, Lijoy K.; Skuli, Nicolas; Mucaj, Vera; Lee, Samuel S.; Zinn, Pascal O.; Sathyan, Pratheesh; Imtiyaz, Hongxia Z.; Zhang, Zhongfa; Davuluri, Ramana V.; Rao, Shilpa; Venneti, Sriram; Lal, Priti; Lathia, Justin D.; Rich, Jeremy; Keith, Brian; Minn, Andy J.; Simon, M. Celeste

doi:10.1073/pnas.1314341111

Cited by 98 publications

(83 citation statements)

References 42 publications

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“…A previous study reported that miR-218 is downregulated in human glioblastoma compared with that in NBTs, and it regulates GBM invasion/migration, proliferation, apoptosis, and stemness by targeting different genes (Tu et al 2013;Song et al 2010;Setty et al 2012;Mathew et al 2014). In this study, we focused on the newly identified relationship between the miR-218 and its other potential target gene, E2F2.…”

Section: Discussionmentioning

confidence: 99%

MiR-218 Inhibited Growth and Metabolism of Human Glioblastoma Cells by Directly Targeting E2F2

et al. 2015

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In recent years, microRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. In this study, we found that miR-218 could inhibit growth and metabolism in gliomas by directly targeting E2F2. First, we obtained data from the Chinese Glioma Genome Atlas (CGGA) database to analyze miR-218 expression in different grades of gliomas. The effects of miR-218 on cell cycle progression and cell proliferation in U87 and U251 cell lines were investigated by flow cytometry, specifically CCK8 assay and tablet cloning, respectively. Glucose consumption and lactate production of glioma cell lines were measured by correlative test kits. Furthermore, we used Western blot analysis and luciferase reporter assay to identify the direct and functional target of miR-218. Data from the CGGA database and real-time quantitative reverse transcription-PCR demonstrated that miR-218 was obviously reduced in human glioblastoma tissues, as well as in the cell lines. When miR-218 level was elevated in vitro, cell cycle progression was arrested in the G1 phase, and cell proliferation was dramatically inhibited. Both glucose consumption and lactate production of glioma cells were significantly reduced. Western blot analysis and luciferase reporter assay revealed that E2F2 was a direct target of miR-218 in glioma cells. This investigation demonstrated that elevated E2F2 expression could partly weaken the effect of miR-218 in vitro. This study also showed that miR-218 may be a repressor in glioma by directly targeting E2F2, as well as a potential therapeutic target in gliomas.

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Section: Discussionmentioning

confidence: 99%

MiR-218 Inhibited Growth and Metabolism of Human Glioblastoma Cells by Directly Targeting E2F2

et al. 2015

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“…necrotic mesenchymal glioblastoma multiforme (GBM), and miR-218 targeted EGF receptor (EGFR) and multiple components of RTKs signaling pathways including PLCγ1, PIK3C2A, and v-raf murine sarcoma 3611 viral oncogene homolog (ARAF) (Mathew et al , 2014). MiR-218 repression up-regulated the abundance and activity of multiple RTK effectors, which elevated RTKs signaling and promoted the activation of HIF, most notably HIF2α.…”

Section: Rtks Signaling-related Mirnasmentioning

confidence: 99%

MicroRNAs in tumor angiogenesis

2015

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“…Recent studies emphasized that manipulation of miRNAs and their oligonucleotide antagonists, including miRNA-based nanodrugs, miRNA mimics, miRNA sponge and miR-mask, represents an attractive approach for antitumor therapy (12,13). In the GBM model, miRNAs could modulate pivotal protein expressions in the signaling cascades, thus, regulate tumor malignant behaviors (14)(15)(16). We propose that by overlapping the datasets of predictive miRNAs targeting CXCR4 and the miRNA profiling between GBM tissues and adjacent normal tissues, we could identify the tumor-specific miRNAs regulating CXCR4 expression in GBMs and offer new miRNA candidates for anti-GBM strategies.…”

Section: Introductionmentioning

confidence: 99%

miR-663 Suppresses Oncogenic Function of CXCR4 in Glioblastoma

Shi

Chen

et al. 2015

Clinical Cancer Research

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Purpose: To identify the miRNA regulators of C-X-C motif chemokine receptor 4 (CXCR4) and the underlying mechanism as well as the therapeutic and prognostic values in human glioblastoma (GBM).Experimental Design: miRNA profile analyses and bioinformatics predictions were used to identify the mediators of CXCR4, which were confirmed by luciferase reporter assay, Western blot assay and immunohistochemistry. The effects of miR-663 on CXCR4-mediated GBM malignancy were investigated by gainof-function experiments. Orthotopic xenografts derived from constitutive or induced miR-663-expressing GBM cells were used to determine the antitumor effects of miR-663 and CXCR4-specific antagonist AMD3100. Bivariate correlation analyses were used to examine the correlation of miR-663 and CXCR4 levels in glioma. The prognostic values of miR-663 and CXCR4 were examined in 281 cases of astrocytic glioma from our hospital and 476 cases of GBM from The Cancer Genome Atlas database using the multivariate Cox regression analysis and Kaplan-Meier analysis.Results: miR-663 negatively regulated CXCR4 expression by targeting its coding sequence in GBM and compromised the proliferative and invasive capacities of GBM cells induced by CXCR4 overexpression. Constitutive or induced miR-663 overexpression combined with CXCR4 antagonist AMD3100 suppressed orthotopic GBM growth and prolonged tumor-bearing mice survival. Clinically, miR-663 and CXCR4 were inversely correlated in GBM and composed a valuable biomarker set in predicting the outcomes of GBM patients.Conclusions: miR-663 negatively regulated CXCR4 to inhibit its oncogenic effect. Combination of miR-663 and CXCR4 can serve as a valuable prognostic biomarker set as well as molecular targets for therapeutic intervention of GBM.

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miR-218 opposes a critical RTK-HIF pathway in mesenchymal glioblastoma

Cited by 98 publications

References 42 publications

MiR-218 Inhibited Growth and Metabolism of Human Glioblastoma Cells by Directly Targeting E2F2

MiR-218 Inhibited Growth and Metabolism of Human Glioblastoma Cells by Directly Targeting E2F2

MicroRNAs in tumor angiogenesis

miR-663 Suppresses Oncogenic Function of CXCR4 in Glioblastoma

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