##plugins.themes.bootstrap3.article.main##

Hamideh Monfared Yavar Jahangard Maryam Nikkhah Seyed Javad Mirnajafi-Zade Seyed Javad Mowla

Abstract

     There are different subtypes of brain tumors, classified according to the origin of the abnormally proliferated glial cells. Glioblastoma multiforma (GBM) is the grade 4 of brain tumors, gliomas, with the least life expectancy. microRNAs (miRNAs) are small, single stranded, non-coding RNAs with 20-25 nt length with post-transcriptional gene regulatory activities. An altered expression of miRNAs is linked to developmental disorders and some diseases, most importantly cancers. miR-21 is a well-known microRNA, overexpressed in almost all cancer types, including brain tumors. It targets several genes with vital roles in cellular pathways involve in proliferation, invasion and metastatic behaviors. Exosomes are 30-100 nm extracellular vesicles which are packed with various molecules, including miRNAs. Here, we suppressed miR-21 expression level in HEK-293T cells by transfecting them with the miRZip-21 vector. However, when U87-MG cells were cultured in the presence of exosomes isolated from conditioned medium of engineered HEK-293T cells derived exosomes, we did not observe any suppressing effect on host cells’ miR-21 expression level. Moreover, by analyzing the effects of miRZip-21-enriched cell’s conditioned media on three other brain cell lines including 1321N1, A-172 and DAOY, cell type-specific effects of exocrine miRZip-21 were revealed. These data suggested that cell lines from different brain tumor subtypes could exert different responses to microRNA-based therapies, based on their cellular origin and clinical behaviors.

Article Details

Keywords

miR-21, Brain tumors, Glioblastoma multiforma, Exosomes

References
Arscott W. T., Tandle A. T., Zhao S., Shabason J. E., Gordon I. K., Schlaff C. D., Zhang G., Tofilon P. J. and Camphausen K. A. J. T. o. (2013) Ionizing radiation and glioblastoma exosomes: implications in tumor biology and cell migration. 6:638-IN636.

Belter A., Rolle K., Piwecka M., Fedoruk-Wyszomirska A., Naskręt-Barciszewska M. Z. and Barciszewski J. J. S. R. (2016) Inhibition of miR-21 in glioma cells using catalytic nucleic acids. 6:24516.

Collino F., Deregibus M. C., Bruno S., Sterpone L., Aghemo G., Viltono L., Tetta C. and Camussi G. J. P. o. (2010) Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. 5:e11803.

Collins V. J. J. o. N., Neurosurgery and Psychiatry. (2004) Brain tumours: classification and genes. 75:ii2-ii11.

Corsten M. F., Miranda R., Kasmieh R., Krichevsky A. M., Weissleder R. and Shah K. J. C. r. (2007) MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell–delivered S-TRAIL in human gliomas. 67:8994-9000.

Devulapally R., Sekar N. M., Sekar T. V., Foygel K., Massoud T. F., Willmann J. r. K. and Paulmurugan R. J. A. n. (2015) Polymer nanoparticles mediated codelivery of antimiR-10b and antimiR-21 for achieving triple negative breast cancer therapy. 9:2290-2302.

Gabriely G., Wurdinger T., Kesari S., Esau C. C., Burchard J., Linsley P. S., Krichevsky A. M. J. M. and biology c. (2008) MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. 28:5369-5380.

Gao F., Zhang P., Zhou C., Li J., Wang Q., Zhu F., Ma C., Sun W. and Zhang L. J. O. r. (2007) Frequent loss of PDCD4 expression in human glioma: possible role in the tumorigenesis of glioma. 17:123-128.

Gaur A. B., Holbeck S. L., Colburn N. H. and Israel M. A. J. N.-o. (2011) Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo. 13:580-590.

Gilbert M. R. 2011. Recurrent glioblastoma: a fresh look at current therapies and emerging novel approaches. In Seminars in oncology. Vol. 38. Elsevier. S21-S33.

Gulyaeva L. F. and Kushlinskiy N. E. J. J. o. t. m. (2016) Regulatory mechanisms of microRNA expression. 14:143.

Gundemir S., Monteagudo A., Akbar A., Keillor J. W. and Johnson G. V. J. N.-o. (2017) The complex role of transglutaminase 2 in glioblastoma proliferation. 19:208-218.

Hayes J., Peruzzi P. P. and Lawler S. J. T. i. m. m. (2014) MicroRNAs in cancer: biomarkers, functions and therapy. 20:460-469.

Huan J., Hornick N. I., Shurtleff M. J., Skinner A. M., Goloviznina N. A., Roberts C. T. and Kurre P. J. C. r. (2013) RNA trafficking by acute myelogenous leukemia exosomes. 73:918-929.

Kramer M. F. J. C. p. i. m. b. (2011) Stem‐loop RT‐qPCR for miRNAs. 95:15.10. 11-15.10. 15.

Kucharzewska P., Christianson H. C., Welch J. E., Svensson K. J., Fredlund E., Ringnér M., Mörgelin M., Bourseau-Guilmain E., Bengzon J. and Belting M. J. P. o. t. N. A. o. S. (2013) Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development.201220998.

Louis D. N., Ohgaki H., Wiestler O. D., Cavenee W. K., Burger P. C., Jouvet A., Scheithauer B. W. and Kleihues P. J. A. n. (2007) The 2007 WHO classification of tumours of the central nervous system. 114:97-109.

Louis D. N., Perry A., Reifenberger G., Von Deimling A., Figarella-Branger D., Cavenee W. K., Ohgaki H., Wiestler O. D., Kleihues P. and Ellison D. W. J. A. n. (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. 131:803-820.

Lu Z., Liu M., Stribinskis V., Klinge C., Ramos K., Colburn N. and Li Y. J. O. (2008) MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. 27:4373.

Malhotra M., Sekar T. V., Ananta J. S., Devulapally R., Afjei R., Babikir H. A., Paulmurugan R. and Massoud T. F. J. O. (2018) Targeted nanoparticle delivery of therapeutic antisense microRNAs presensitizes glioblastoma cells to lower effective doses of temozolomide in vitro and in a mouse model. 9:21478.

Mittelbrunn M., Gutiérrez-Vázquez C., Villarroya-Beltri C., González S., Sánchez-Cabo F., González M. Á., Bernad A. and Sánchez-Madrid F. J. N. c. (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. 2:282.

Nouraee N., Mowla S. J., Calin G. A. J. G., Chromosomes and Cancer. (2015) Tracking miRNAs' footprints in tumor–microenvironment interactions: insights and implications for targeted cancer therapy. 54:335-352.

Nouraee N., Van Roosbroeck K., Vasei M., Semnani S., Samaei N. M., Naghshvar F., Omidi A. A., Calin G. A. and Mowla S. J. J. P. O. (2013) Expression, tissue distribution and function of miR-21 in esophageal squamous cell carcinoma. 8:e73009.

Ogata-Kawata H., Izumiya M., Kurioka D., Honma Y., Yamada Y., Furuta K., Gunji T., Ohta H., Okamoto H. and Sonoda H. J. P. o. (2014) Circulating exosomal microRNAs as biomarkers of colon cancer. 9:e92921.

Paolillo M., Boselli C. and Schinelli S. J. B. s. (2018) Glioblastoma under siege: an overview of current therapeutic strategies. 8:15.

Papagiannakopoulos T., Shapiro A. and Kosik K. S. J. C. r. (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. 68:8164-8172.

Paul P., Chakraborty A., Sarkar D., Langthasa M., Rahman M., Bari M., Singha R. S., Malakar A. K. and Chakraborty S. J. J. o. c. p. (2018) Interplay between miRNAs and human diseases. 233:2007-2018.

Ratajczak J., Wysoczynski M., Hayek F., Janowska-Wieczorek A. and Ratajczak M. J. L. (2006) Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. 20:1487.

Sekar D., Saravanan S., Karikalan K., Thirugnanasambantham K., Lalitha P. and IH Islam V. J. C. p. b. (2015) Role of microRNA 21 in mesenchymal stem cell (MSC) differentiation: a powerful biomarker in MSCs derived cells. 16:43-48.

Sicard F., Gayral M., Lulka H., Buscail L. and Cordelier P. J. M. T. (2013) Targeting miR-21 for the therapy of pancreatic cancer. 21:986-994.

Tanaka Y., Kamohara H., Kinoshita K., Kurashige J., Ishimoto T., Iwatsuki M., Watanabe M. and Baba H. J. C. (2013) Clinical impact of serum exosomal microRNA‐21 as a clinical biomarker in human esophageal squamous cell carcinoma. 119:1159-1167.

Théry C., Amigorena S., Raposo G. and Clayton A. J. C. p. i. c. b. (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. 30:3.22. 21-23.22. 29.

Tian T., Zhu Y.-L., Zhou Y.-Y., Liang G.-F., Wang Y.-Y., Hu F.-H. and Xiao Z.-D. J. J. o. B. C. (2014) Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery.jbc. M114. 588046.

Tkach M. and Théry C. J. C. (2016) Communication by extracellular vesicles: where we are and where we need to go. 164:1226-1232.

Toll L., Jimenez L., Waleh N., Jozwiak K., Woo A.-H., Xiao R.-P., Bernier M., Wainer I. J. J. o. P. and Therapeutics E. (2011) β2-adrenergic receptor agonists inhibit the proliferation of 1321N1 astrocytoma cells. 336:524-532.

Tsukamoto M., Iinuma H., Yagi T., Matsuda K. and Hashiguchi Y. J. O. (2017) Circulating exosomal microRNA-21 as a biomarker in each tumor stage of colorectal cancer. 92:360-370.

Van Meir E. G., Hadjipanayis C. G., Norden A. D., Shu H. K., Wen P. Y. and Olson J. J. J. C. a. c. j. f. c. (2010) Exciting new advances in neuro‐oncology: the avenue to a cure for malignant glioma. 60:166-193.

Verhaak R. G., Hoadley K. A., Purdom E., Wang V., Qi Y., Wilkerson M. D., Miller C. R., Ding L., Golub T. and Mesirov J. P. J. C. c. (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. 17:98-110.

Wang J.-J., Wang Z.-Y., Chen R., Xiong J., Yao Y.-L., Wu J.-H. and Li G.-X. J. A. P. J. C. P. (2015) Macrophage-secreted exosomes delivering miRNA-21 inhibitor can regulate BGC-823 cell proliferation.16:4203-4209.

Yang C. H., Yue J., Pfeffer S. R., Fan M., Paulus E., Hosni-Ahmed A., Sims M., Qayyum S., Davidoff A. M. and Handorf C. R. J. J. o. B. C. (2014) MicroRNA-21 promotes glioblastoma tumorigenesis by down-regulating insulin-like growth factor-binding protein-3 (IGFBP3). 289:25079-25087.

Yu X., Odenthal M. and Fries J. W. J. I. j. o. m. s. (2016) Exosomes as miRNA carriers: formation–function–future. 17:2028.

Yuana Y., Sturk A. and Nieuwland R. J. B. r. (2013) Extracellular vesicles in physiological and pathological conditions. 27:31-39.

Zhang J., Li S., Li L., Li M., Guo C., Yao J., Mi S. J. G., proteomics and bioinformatics. (2015) Exosome and exosomal microRNA: trafficking, sorting, and function. 13:17-24.
How to Cite
Hamideh, M., Yavar, J., Maryam, N., Seyed Javad, M.-Z., & Seyed Javad, M. (2019). Cell type-specific Effect of miRZip-21 to Suppress miR-21 in Human Glioma Cell Lines. Journal of Cell and Molecular Research, 10(2), 59-66. https://doi.org/10.22067/jcmr.v10i2.76835
Section
Research Articles