Abstract
MicroRNAs can function as oncogenes or tumor suppressors in glioma. Previously, we showed that miR-107 inhibits glioma cell proliferation, migration, and invasion. Since tumor growth and invasion are closely related to angiogenesis, we further examined the role of miR-107 in glioma angiogenesis. In a co-culture of glioma cells and human brain microvascular endothelial cells (HBMVEC), overexpression of miR-107 in glioma cells led to the inhibition of HBMVEC proliferation, migration, and tube formation ability. ELISA, RT-PCR, and western blot assays revealed that upregulation of miR-107 in glioma cells inhibits VEGF expression. Our findings collectively support the critical involvement of miR-107 in glioma cell angiogenesis and highlight its potential as a therapeutic target for glioma.
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References
Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Brandes AA, Franceschi E, Gorlia T, Wick W, Jacobs AH, Baumert BG, van den Bent M, Weller M, Stupp R (2012) Appropriate end-points for right results in the age of antiangiogenic agents: future options for phase II trials in patients with recurrent glioblastoma. Eur J Cancer 48:896–903
Chen L, Chen XR, Zhang R, Li P, Liu Y, Yan K, Jiang XD (2013a) MicroRNA-107 inhibits glioma cell migration and invasion by modulating Notch2 expression. J Neurooncol 112:59–66
Chen L, Zhang R, Li P, Liu Y, Qin K, Fa ZQ, Liu YJ, Ke YQ, Jiang XD (2013b) P53-induced microRNA-107 inhibits proliferation of glioma cells and down-regulates the expression of CDK6 and Notch-2. Neurosci Lett 534:327–332
Cohen AL, Colman H (2015) Glioma biology and molecular markers. Cancer Treat Res 163:15–30
Gaur AB, Holbeck SL, Colburn NH, Israel MA (2011) Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo. Neuro-oncology 13:580–590
Grau SJ, Trillsch F, Herms J, Thon N, Nelson PJ, Tonn JC, Goldbrunner R (2007) Expression of VEGFR3 in glioma endothelium correlates with tumor grade. J Neurooncol 82:141–150
Jenny B, Harrison JA, Baetens D, Tille JC, Burkhardt K, Mottaz H, Kiss JZ, Dietrich PY, De Tribolet N, Pizzolato GP, Pepper MS (2006) Expression and localization of VEGF-C and VEGFR-3 in glioblastomas and haemangioblastomas. J Pathol 209:34–43
Kurz H, Korn J, Eggli PS, Huang R, Christ B (2001) Embryonic central nervous system angiogenesis does not involve blood-borne endothelial progenitors. J Comp Neurol 436:263–274
Li Y, Li W, Yang Y, Lu Y, He C, Hu G, Liu H, Chen J, He J, Yu H (2009) MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme. Brain Res 1286:13–18
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109
Mendell JT (2008) miRiad roles for the miR-17-92 cluster in development and disease. Cell 133:217–222
Plate KH, Breier G, Risau W (1994) Molecular mechanisms of developmental and tumor angiogenesis. Brain Pathol 4:207–218
Qian X, Zhao P, Li W, Shi ZM, Wang L, Xu Q, Wang M, Liu N, Liu LZ, Jiang BH (2013) MicroRNA-26a promotes tumor growth and angiogenesis in glioma by directly targeting prohibitin. CNS Neurosci Ther 19:804–812
Ren Y, Zhou X, Mei M, Yuan XB, Han L, Wang GX, Jia ZF, Xu P, Pu PY, Kang CS (2010) MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol. BMC Cancer 10:27
Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674
Shi ZM, Wang J, Yan Z, You YP, Li CY, Qian X, Yin Y, Zhao P, Wang YY, Wang XF, Li MN, Liu LZ, Liu N, Jiang BH (2012) MiR-128 inhibits tumor growth and angiogenesis by targeting p70S6K1. PLoS ONE 7:e32709
Shyu AB, Wilkinson MF, van Hoof A (2008) Messenger RNA regulation: to translate or to degrade. EMBO J 27:471–481
Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, de Witt Hamer PC, Marquez VE, Cloos J, Krichevsky AM, Noske DP, Tannous BA, Wurdinger T (2010) miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. Oncotarget 1:710–720
Smits M, Wurdinger T, van het Hof B, Drexhage JA, Geerts D, Wesseling P, Noske DP, Vandertop WP, de Vries HE, Reijerkerk A (2012) Myc-associated zinc finger protein (MAZ) is regulated by miR-125b and mediates VEGF-induced angiogenesis in glioblastoma. FASEB J 26:2639–2647
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996
Sun L, Yan W, Wang Y, Sun G, Luo H, Zhang J, Wang X, You Y, Yang Z, Liu N (2011) MicroRNA-10b induces glioma cell invasion by modulating MMP-14 and uPAR expression via HOXD10. Brain Res 1389:9–18
Volpert OV, Dameron KM, Bouck N (1997) Sequential development of an angiogenic phenotype by human fibroblasts progressing to tumorigenicity. Oncogene 14:1495–1502
Weis SM, Cheresh DA (2011) Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med 17:1359–1370
Wurdinger T, Tannous BA, Saydam O, Skog J, Grau S, Soutschek J, Weissleder R, Breakefield XO, Krichevsky AM (2008) miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell 14:382–393
Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309:1519–1524
Zhang B, Pan X, Cobb GP, Anderson TA (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302:1–12
Acknowledgments
This project was supported by the Postdoctoral Science Foundation of China (2014M552271) and the Natural Science Foundation of Guangdong (2014A030310057).
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Lei Chen and Zong-yang Li have contributed equally to this work.
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Chen, L., Li, Zy., Xu, Sy. et al. Upregulation of miR-107 Inhibits Glioma Angiogenesis and VEGF Expression. Cell Mol Neurobiol 36, 113–120 (2016). https://doi.org/10.1007/s10571-015-0225-3
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DOI: https://doi.org/10.1007/s10571-015-0225-3