Identification and Functional Characterization of microRNAs Involved in the Malignant Progression of Gliomas
Article first published online: 19 AUG 2009
© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
Volume 20, Issue 3, pages 539–550, May 2010
How to Cite
Malzkorn, B., Wolter, M., Liesenberg, F., Grzendowski, M., Stühler, K., Meyer, H. E. and Reifenberger, G. (2010), Identification and Functional Characterization of microRNAs Involved in the Malignant Progression of Gliomas. Brain Pathology, 20: 539–550. doi: 10.1111/j.1750-3639.2009.00328.x
- Issue published online: 12 APR 2010
- Article first published online: 19 AUG 2009
- Received 20 May 2009; accepted 10 August 2009.
- glioma progression;
- miR-17-92 cluster;
Diffuse astrocytoma of World Health Organization (WHO) grade II has an inherent tendency to spontaneously progress to anaplastic astrocytoma WHO grade III or secondary glioblastoma WHO grade IV. We explored the role of microRNAs (miRNAs) in glioma progression by investigating the expression profiles of 157 miRNAs in four patients with primary WHO grade II gliomas that spontaneously progressed to WHO grade IV secondary glioblastomas. Thereby, we identified 12 miRNAs (miR-9, miR-15a, miR-16, miR-17, miR-19a, miR-20a, miR-21, miR-25, miR-28, miR-130b, miR-140 and miR-210) showing increased expression, and two miRNAs (miR-184 and miR-328) showing reduced expression upon progression. Validation experiments on independent series of primary low-grade and secondary high-grade astrocytomas confirmed miR-17 and miR-184 as promising candidates, which were selected for functional analyses. These studies revealed miRNA-specific influences on the viability, proliferation, apoptosis and invasive growth properties of A172 and T98G glioma cells in vitro. Using mRNA and protein expression profiling, we identified distinct sets of transcripts and proteins that were differentially expressed after inhibition of miR-17 or overexpression of miR-184 in glioma cells. Taken together, our results support an important role of altered miRNA expression in gliomas, and suggest miR-17 and miR-184 as interesting candidates contributing to glioma progression.