MicroRNA involvement in glioblastoma pathogenesis.

MicroRNAs are endogenously expressed regulatory noncoding RNAs. Altered expression levels of several microRNAs have been observed in glioblastomas. Functions and direct mRNA targets for these microRNAs have been relatively well studied over the last years. According to these data, it is now evident, that impairment of microRNA regulatory network is one of the key mechanisms in glioblastoma pathogenesis. MicroRNA deregulation is involved in processes such as cell proliferation, apoptosis, cell cycle regulation, invasion, glioma stem cell behavior, and angiogenesis. In this review, we summarize the current knowledge of miRNA functions in glioblastoma with an emphasis on its significance in glioblastoma oncogenic signaling and its potential to serve as a disease biomarker and a novel therapeutic target in oncology.

[1]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[2]  P. Kleihues,et al.  Genetic pathways to primary and secondary glioblastoma. , 2007, The American journal of pathology.

[3]  A. Bradley,et al.  Identification of mammalian microRNA host genes and transcription units. , 2004, Genome research.

[4]  I. Lorimer,et al.  Regulation of p27Kip1 by miRNA 221/222 in Glioblastoma , 2007, Cell cycle.

[5]  Agnieszka Bronisz,et al.  Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. , 2008, Cancer research.

[6]  Junxia Zhang,et al.  hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells , 2008, Brain Research.

[7]  Wei Liu,et al.  MicroRNA-21 down-regulates the expression of tumor suppressor PDCD4 in human glioblastoma cell T98G. , 2008, Cancer letters.

[8]  J. Zalvide,et al.  Inhibition of Cdk4 Activity Enhances Translation of p27 kip1 in Quiescent Rb-negative Cells* , 2003, The Journal of Biological Chemistry.

[9]  W. Cho OncomiRs: the discovery and progress of microRNAs in cancers , 2007, Molecular Cancer.

[10]  P. Kleihues,et al.  Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. , 2005, Journal of neuropathology and experimental neurology.

[11]  Paola Pisani,et al.  Genetic Pathways to Glioblastoma , 2004, Cancer Research.

[12]  T. Maniatis,et al.  The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. , 2007, Molecular cell.

[13]  Claudia Petritsch,et al.  miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells , 2008 .

[14]  E. Parati,et al.  Neurosphere and neurosphere-forming cells: morphological and ultrastructural characterization , 2003, Brain Research.

[15]  Francesco Tomasello,et al.  miR-21 and 221 upregulation and miR-181b downregulation in human grade II–IV astrocytic tumors , 2009, Journal of Neuro-Oncology.

[16]  K. Ghoshal,et al.  MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. , 2007, Gastroenterology.

[17]  Shuomin Zhu,et al.  MicroRNA-21 targets tumor suppressor genes in invasion and metastasis , 2008, Cell Research.

[18]  Alice Shapiro,et al.  MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. , 2008, Cancer research.

[19]  T. Wurdinger,et al.  MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators , 2008, Molecular and Cellular Biology.

[20]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[21]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[22]  R. Weinberg,et al.  Tumour invasion and metastasis initiated by microRNA-10b in breast cancer , 2007, Nature.

[23]  K. Kosik,et al.  MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. , 2005, Cancer research.

[24]  Y. Okada,et al.  The role of matrix metalloproteinases in glioma invasion. , 2003, Frontiers in bioscience : a journal and virtual library.

[25]  B. Samans,et al.  Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1). , 2004, American journal of physiology. Cell physiology.

[26]  Wei Liu,et al.  MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a , 2008, Journal of Molecular Medicine.

[27]  G. Maira,et al.  Extensive modulation of a set of microRNAs in primary glioblastoma. , 2005, Biochemical and biophysical research communications.

[28]  D. Louis WHO classification of tumours of the central nervous system , 2007 .

[29]  Gideon Rechavi,et al.  MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cells. , 2008, Biochemical and biophysical research communications.

[30]  G. Maira,et al.  Regulation of the p 27 Kip 1 tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation , 2007 .

[31]  Goberdhan P Dimri,et al.  Control of the Replicative Life Span of Human Fibroblasts by p16 and the Polycomb Protein Bmi-1 , 2003, Molecular and Cellular Biology.

[32]  Sam Griffiths-Jones,et al.  The microRNA Registry , 2004, Nucleic Acids Res..

[33]  Reuven Agami,et al.  Regulation of the p27Kip1 tumor suppressor by miR‐221 and miR‐222 promotes cancer cell proliferation , 2007 .

[34]  Birgit Samans,et al.  Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21Waf1/Cip1 , 2004 .

[35]  Y. Yonekawa,et al.  Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. , 1996, Brain pathology.

[36]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[37]  J. Cui,et al.  Up-regulation of micro-RNA-221 (miRNA-221; chr Xp11.3) and caspase-3 accompanies down-regulation of the survivin-1 homolog BIRC1 (NAIP) in glioblastoma multiforme (GBM) , 2008, Journal of Neuro-Oncology.

[38]  H. Allgayer,et al.  MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer , 2008, Oncogene.

[39]  S. Morrison,et al.  Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. , 2005, Genes & development.

[40]  V. Ambros,et al.  Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation , 2004, Genome Biology.

[41]  B. Scheithauer,et al.  The 2007 WHO classification of tumours of the central nervous system , 2007, Acta Neuropathologica.

[42]  Yunqing Li,et al.  microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. , 2008, Cancer research.