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    The vast majority of the human genome is transcribed into noncoding RNAs. Among these, microRNAs (miRNA) and long noncoding RNAs (lncRNA) are frequently deregulated in cancer, where they regulate a wide variety of functions. Glioblastoma (GBM) is the most common and the most deadly primary human brain tumor. This chapter reviews the deregulation, functions, mechanisms of action, and clinical applications of miRNAs and lncRNAs in GBM. miRNAs are short noncoding RNAs that broadly and profoundly regulate gene expression. Numerous miRNAs are deregulated in GBM, where their expression levels can serve as diagnostic and prognostic biomarkers. miRNAs can act as oncogenes or tumor suppressors in GBM by regulating the expression of numerous tumor-suppressive or oncogenic proteins. miRNAs regulate all GBM malignancy parameters including tumor cell proliferation, cell survival, invasion, angiogenesis, cancer stem cells, immune escape, and therapy resistance. miRNAs are also secreted in body fluids, where they can be used as biomarkers. Because of their deep involvement in GBM malignancy, efforts are under way to also exploit miRNAs as therapeutic agents or targets. lncRNAs are a diverse group of noncoding RNAs that are >200 nucleotides long. Several lncRNAs are deregulated in GBM, where their expressions can associate with clinical parameters. lncRNAs regulate GBM functions including tumor cell proliferation, survival, invasion, cancer stem cell differentiation, and therapy resistance. lncRNAs exert their actions via transcriptional, post-transcriptional, and epigenetic mechanisms that are only partly understood. Studying noncoding RNAs is important for the understanding, management, and development of future therapies for GBM.
    6 years ago by @marcsaric
     
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      Glioblastoma (GBM, WHO grade IV astrocytoma) is among the most common adult brain tumors and one that is invariably fatal. GBM is classified as either primary (de novo) or secondary in origin. Secondary GBMs are derived from previously lower grade (WHO grades II or III) gliomas. While secondary GBMs present with similar clinical characteristics as their primary counterparts, the molecular pathways involved in their pathogenesis distinguish the two and have functional consequences for their behavior. Although a large number of histologic markers are routinely utilized to distinguish primary from secondary GBM, advances in genomic and bioinformatics techniques have drastically improved classification of high-grade gliomas and our understanding of the molecular pathways that influence tumor behavior and response to treatment. The significant influence of molecular identity on tumor behavior has been recognized by the most recent WHO classification of CNS tumors, wherein specific molecular markers have been integrated as part of tumor subtype identification process, as a supplement to traditional histological analysis. Indeed, the change heralds a new era for neuro-oncology, one that is moving toward targeted therapeutics as part of the standard of care. Thus, a comprehensive grasp of this diverse landscape is necessary. In this chapter, we provide an overview of our latest understanding of the molecular diversity of GBM, specifically as it pertains to primary and secondary GBMs, and how it influences prognostication and therapeutic decision-making.
      7 years ago by @marcsaric
       
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