Abstract
Astrocytic gliomas are the most common type of human primary brain tumors with poor prognosis. MicroRNAs(miRs) are frequently deregulated in gliomas and play an oncogenic or tumor suppressor role. In our previous study we found that miR-19a and miR-19b were up-regulated in malignant glioma cell lines by microRNA array. For further validation of this finding, the expression of miR-19a and miR-19b was detected by qRT-PCR and in situ hybridization(ISH) in 8 malignant glioma cell lines, 43 freshly resected glioma samples and 75 archival paraffin embedded glioma specimens with different grades of malignancy in the present study. The results demonstrate that miR-19a and miR-19b are overexpressed in glioma cell lines and astrocytic glioma tissues, and their expression level is positively correlated with tumor grades. Additionally, the tumor suppressor gene PTEN is identified as the target of miR-19a and miR-19b by Luciferase assay. It is speculated that miR-19a and miR-19b may have an oncogenic role in gliomagenesis at least partially via the negative regulation of PTEN and the molecular mechanism of gliomagenesis in which miR 19a and miR-19b involved should be investigated further.
Similar content being viewed by others
References
Louis DN (2006) Molecular pathology of malignant gliomas. Annu Rev Pathol 1:97–117
Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996
Chen L, Li C, Zhang R et al (2011) miR-17-92 cluster microRNAs confers tumorigenicity in multiple myeloma. Cancer Lett 309(1):62–70
Takakura S, Mitsutake N, Nakashima M et al (2008) Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci 99(6):1147–1154
Ruan JS, Chen HZ, Kurgan L et al (2008) HuMiTar: a sequence-based method for prediction of human microRNA targets. Algorithm Mol Biol 3:16
You Y, Pu P, Huang Q et al (2006) Antisense telomerase RNA inhibits the growth of human glioma cells in vitro and in vivo. Int J Oncol 28:1225–1232
Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033
Zhang Y, Dutta A, Abounader R (2012) The role of microRNAs in glioma initiation and progression. Front Biosci 17:700–712
Ota A, Tagawa H, Karnan S et al (2004) Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res 64:3087–3095
Hayashita Y, Osada H, Tatematsu Y et al (2005) A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65:9628–9632
Tagawa H, Karube K, Tsuzuki S et al (2007) Synergistic action of the microRNA-17 poly-cistron and Myc in aggressive cancer development. Cancer Sci 98:1482–1490
Liang Z, Li Y, Huang K et al (2011) Regulation of miR-19 to breast cancer chemoresistance through targeting PTEN. Pharm Res 28(12):3091–3100
Ye H, Liu X, Lv M et al (2012) MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia. Nucleic Acids Res 40(12):5201–5214
Baraniskin A, Kuhnhenn J, Schlegel U et al (2011) Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood 117(11):3140–3146
Conkrite K, Sundby M, Mukai S et al (2011) miR-17-92 cooperates with RB pathway mutations to promote retinoblastoma. Genes Dev 25(16):1734–1745
Zhang X, Yu H, Lou JR et al (2011) MicroRNA-19 (miR-19) regulates tissue factor expression in breast cancer cells. J Biol Chem 286(2):1429–1435
Mavrakis KJ, Wolfe AL, Oricchio E, Palomero T et al (2010) Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol 12(4):372–379
Ping M, Han Y-C, Bete D et al (2009) Genetic dissection of the miR-17-92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev 23(24):2806–2811
Grillari J, Hackl M, Grillari-Voglauer R (2010) miR-17-92 cluster: ups and downs in cancer and aging. Biogerontology 11(4):501–506
Acknowledgments
This work was supported by National Natural Science Foundation of China (Grant No:81101915, Grant No: 30872985), Tianjin Health Service Science and Technique Foundation(Grant No: 2011KZ109)
Conflict of Interest
The authors have not conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Zhifan Jia and Wang Kun contribute equally to this work.
Rights and permissions
About this article
Cite this article
Jia, Z., Wang, K., Zhang, A. et al. miR-19a and miR-19b Overexpression in Gliomas. Pathol. Oncol. Res. 19, 847–853 (2013). https://doi.org/10.1007/s12253-013-9653-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12253-013-9653-x