miRNA
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A brain tumor is any intracranial tumor created by abnormal and uncontrolled cell division, normally either found in the brain itself, in the cranial nerves, in the brain envelopes, skull, pituitary and pineal gland, or spread from cancers primarily located in other organs. Primary (true) brain tumors are commonly located in the posterior cranial fossa in children and in the anterior two-thirds of the cerebral hemispheres in adults, although they can affect any part of the brain. The most frequent and malignant of primary brain tumors, glioblastoma multiforme (GBM), has received significant attention from the research community as these tumors are highly invasive, very aggressive, and typically exhibit a poor prognosis despite improvements in surgical and radiotherapeutic techniques. Although a number of genetic and molecular lesions have been correlated to GBM progression, critical analysis of this tumor is still needed to gain clarity on disease progression and treatment options. Traditionally, miRNA expression has been tested using low-throughput techniques such as Northern-blot analysis and real-time PCR, but new developments in microarray technology now enable global profiling of all miRNA genes and their precursors in any sample type.
S.A. Ciafre et al (2005) examined by microarray, and confirmed by Northern blot analysis, 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 the group to identify a group of microRNAs whose expression was significantly altered in this tumor.
Title: Extensive modulation of a set of microRNAs in primary glioblastoma.
Authors: Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG
Journal: Biochem Biophys Res Commun, Vol 334, Issue 4: 1351-8
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Although knowledge of the specific mRNA targets for known mammalian miRNAs is limited, one emerging function of this extensive regulatory network is its control over processes that underlie cell proliferation and differentiation in diverse organisms during normal development. Chan and colleagues (2005) examined the expression of miR-21 in glioblastoma multiforme, demonstrating a correlation between miR-21expression and restriction of apoptosis in cultured glioblastoma multiforme cells. The group combined Northern blot and microarray analysis for gaining identification and expression information for miR-21, and transformation followed by apoptosis assays to determine the effects of miR-21 as an antiapoptotic factor.
Title: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells.
Authors: Chan JA, Krichevsky AM, Kosik KS
Journal: Cancer Res, Vol 65, Issue 14: 6029-33
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Until recently, expression profiling of miRNAs has not included in situ hybridization of human miRNAs and has only been performed in conjunction with fresh tissues. Peter Nelson and researchers (2006) coordinated miRNA expression analysis from the tissue level to the subcellular level, using the RAKE (RNA-primed, array-based, Klenow Enzyme) miRNA microarray platform in conjunction with Locked Nucleic Acid (LNA)-based in situ hybridization (LNA-ISH) on archival FFPE human brains and oligodendroglial tumors, opening the door to analysis on previously stored samples. This study revealed particular miRNAs that are expressed in normal human brain and in oligodendrogliomas. Further, in situ hybridization was applied successfully to refine the data obtained by RAKE and to localize particular miRNAs, indicating the remarkable stability of miRNAs in archival human tissues and the importance of future analysis on these preserved samples.
Title: RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain.
Authors: Nelson PT, Baldwin DA, Kloosterman WP, Kauppinen S, Plasterk RH, Mourelatos Z
Journal: RNA, Vol 12, Issue 2: 187-91
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Title: RNAi based approaches to the treatment of malignant glioma.
Authors: Mathupala SP, Guthikonda M, Sloan AE
Journal: Technol Cancer Res Treat, Vol 5, Issue 3: 261-9
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Title: Chromosomal translocations fusing the BCL6 gene to different partner loci are recurrent in primary central nervous system lymphoma and may be associated with aberrant somatic hypermutation or defective class switch recombination.
Authors: Schwindt H, Akasaka T, Zuhlke-Jenisch R, Hans V, Schaller C, Klapper W, Dyer MJ, Siebert R, Deckert M
Journal: J Neuropathol Exp Neurol, Vol 65, Issue 8: 776-82
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Title: Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation.
Authors: Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V
Journal: Genome Biol, Vol 5, Issue 3: R13
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