MicroRNA Targeting as a Therapeutic Strategy Against Glioma

Auffinger, Brenda; Thaçi, Bart; Ahmed, Amiya; Ulasov, Ilya V.; Lesniak, Maciej S.

doi:10.2174/1566524011313040006

Cited by 30 publications

(22 citation statements)

References 60 publications

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“…Studies have demonstrated that miRNAs influence the response to chemotherapies for ovarian cancer, pancreatic cancer, bladder cancer and glioblastoma [37-40]. In a study conducted by Liana Adam, miR-200 expression regulated the epithelial-to-mesenchymal transition in bladder cancer cells and reversed EGFR therapy resistance [41].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab

et al. 2014

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BackgroundEpidermal growth factor receptor (EGFR) is amplified in 40% of human glioblastomas. However, most glioblastoma patients respond poorly to anti-EGFR therapy. MicroRNAs can function as either oncogenes or tumor suppressor genes, and have been shown to play an important role in cancer cell proliferation, invasion and apoptosis. Whether microRNAs can impact the therapeutic effects of EGFR inhibitors in glioblastoma is unknown.MethodsmiR-566 expression levels were detected in glioma cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate VHL as a direct target gene of miR-566. Cell proliferation, invasion, cell cycle distribution and apoptosis were also examined to confirm whether miR-566 inhibition could sensitize anti-EGFR therapy.ResultsIn this study, we demonstrated that miR-566 is up-regulated in human glioma cell lines and inhibition of miR-566 decreased the activity of the EGFR pathway. Lentiviral mediated inhibition of miR-566 in glioblastoma cell lines significantly inhibited cell proliferation and invasion and led to cell cycle arrest in the G0/G1 phase. In addition, we identified von Hippel-Lindau (VHL) as a novel functional target of miR-566. VHL regulates the formation of the β-catenin/hypoxia-inducible factors-1α complex under miR-566 regulation.ConclusionsmiR-566 activated EGFR signaling and its inhibition sensitized glioblastoma cells to anti-EGFR therapy.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab

et al. 2014

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“…9 Yet, functional delivery of these targeted treatments without the use of viral vectors is yet to be successful. Cell-based delivery mechanisms have become an attractive method for delivering miR and anti-miR for therapies, particularly through stem cells, due to their tropism to the region of GBM cells.…”

Section: Introductionmentioning

confidence: 99%

Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell–derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity

Munoz

Bliss

Greco

et al. 2013

Molecular Therapy - Nucleic Acids

446

313

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Glioblastoma multiforme (GBM), the most common and lethal tumor of the adult brain, generally shows chemo- and radioresistance. MicroRNAs (miRs) regulate physiological processes, such as resistance of GBM cells to temozolomide (TMZ). Although miRs are attractive targets for cancer therapeutics, the effectiveness of this approach requires targeted delivery. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM. We report on an increase in miR-9 in TMZ-resistant GBM cells. miR-9 was involved in the expression of the drug efflux transporter, P-glycoprotein. To block miR-9, methods were developed with Cy5-tagged anti-miR-9. Dye-transfer studies indicated intracellular communication between GBM cells and MSCs. This occurred by gap junctional intercellular communication and the release of microvesicles. In both cases, anti-miR-9 was transferred from MSCs to GBM cells. However, the major form of transfer occurred with the microvesicles. The delivery of anti-miR-9 to the resistant GBM cells reversed the expression of the multidrug transporter and sensitized the GBM cells to TMZ, as shown by increased cell death and caspase activity. The data showed a potential role for MSCs in the functional delivery of synthetic anti-miR-9 to reverse the chemoresistance of GBM cells.

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“…To our knowledge, a growing body of evidence indicates that miRNAs play fundamental roles in the tumorigenesis of human cancer including glioma, affecting cell survival, proliferation, differentiation, metabolism, angiogenesis, and stem cell generation [3, 4]. More and more numbers of miRNAs including miR-21, miR-125b, let-7, miR-9, and miR-137, as tumor suppressors or oncogenes by negatively regulating oncogenes or tumor-suppressor genes, have been verified to expose aberrant expression in glioma [5–9].…”

Section: Introductionmentioning

confidence: 99%

MiR-15b Targets Cyclin D1 to Regulate Proliferation and Apoptosis in Glioma Cells

Sun

Shi

Yan³

et al. 2014

BioMed Research International

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Aim. To investigate the role and mechanism of miR-15b in the proliferation and apoptosis of glioma. Methods. The miR-15b mimics were transfected into human glioma cells to upregulate the miR-15b expression. Cyclin D1 was determined by both western blotting analysis and luciferase reporter assay. Methylthiazol tetrazolium (MTT) and flow cytometry were employed to detect the cell proliferation, cell cycle, and apoptosis. Results. Overexpression of miR-15b inhibits proliferation by arrested cell cycle progression and induces apoptosis, possibly by directly targeting Cyclin D1. Both luciferase assay and bioinformatics search revealed a putative target site of miR-15b binding to the 3′-UTR of Cyclin D1. Moreover, expression of miR-15b in glioma tissues was found to be inversely correlated with Cyclin D1 expression. Enforced Cyclin D1 could abrogate the miR-15b-mediated cell cycle arrest and apoptosis. Conclusions. Our findings identified that miR-15b may function as a glioma suppressor by targeting the Cyclin D1, which may provide a novel therapeutic strategy for treatment of glioma.

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MicroRNA Targeting as a Therapeutic Strategy Against Glioma

Cited by 30 publications

References 60 publications

MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab

MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab

Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell–derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity

MiR-15b Targets Cyclin D1 to Regulate Proliferation and Apoptosis in Glioma Cells

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