Extensive modulation of a set of microRNAs in primary glioblastoma

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Abstract

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles in animals and plants by repressing translation or cleaving RNA transcripts. The specific modulation of several microRNAs has been recently associated to some forms of human cancer, suggesting that these short molecules may represent a new class of genes involved in oncogenesis. In our study, we examined by microarray the global expression levels of 245 microRNAs in glioblastoma multiforme, the most frequent and malignant of primary brain tumors. The analysis of both glioblastoma tissues and glioblastoma cell lines allowed us to identify a group of microRNAs whose expression is significantly altered in this tumor. The most interesting results came from miR-221, strongly up-regulated in glioblastoma and from a set of brain-enriched miRNAs, miR-128, miR-181a, miR-181b, and miR-181c, which are down-regulated in glioblastoma.

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Materials and methods

RNA isolation from tissue samples and cell lines. Tissue samples were obtained after informed consent from adult patients diagnosed with glioblastoma de novo, one astrocytoma grade II, and one oligoastrocytoma grade III, freshly resected during surgery and immediately frozen in liquid nitrogen for subsequent total RNA extraction. RNA was isolated from tissues and cell lines using Trizol reagent (Invitrogen, Carlsbad, CA) according to the manufacturer’s instructions. Human cell lines used in

Results and discussion

To investigate whether miRNAs are differentially expressed in glioblastoma versus normal brain tissue, we performed a microarray analysis using a microarray chip able to examine global expression levels of 245 miRNAs [16]; the chip also enabled to distinguish between the mature and precursor form (pre-miRNA) of 76 microRNA sequences.

By this method, we analyzed tissue samples from nine primary glioblastoma patients (five female and four male). In order to yield a very specific, case by case

Acknowledgments

This study was funded in part by grants from the Italian Ministry of Instruction, University and Scientific Research (MIUR), FIRB 2001 and CNR-MIUR “Progetto Oncologia,” to M.G.F. and to G.M., by Associazione Italiana per la Ricerca sul Cancro (AIRC), by Ministero dell’Istruzione, dell’Università e della Ricerca by Ministero della Salute Italiano and by Progetto CAN2005—Comitato dei Sostenitori to M.N., by Program Project Grant P01CA76259, P01CA81534, and CA083698 to C.M.C from the National

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    These two authors contributed equally to this work.

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