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MicroRNAs and CancerMaher, S.G., Bibby, B.A.S., Moody, Hannah L., Reid, G. January 2015 (has links)
No / MicroRNAs are a relatively new class of small, noncoding RNA species that represent a cornerstone of cell biology, with diverse roles ranging from embryonic development to aging. miRNAs function to regulate posttranscriptional gene expression, are critical to the normal function of cells, and as such are frequently dysregulated during disease processes. In this chapter, we discuss the biogenesis and mechanism of action of miRNA and their role in cancer initiation, promotion, and progression. In addition, we discuss the most recently identified dual roles of miRNA in epigenetic gene regulation; how they are both regulators and regulated. Finally, we discuss the emerging roles of miRNA as epigenetic anti-cancer therapeutics, the current research examining inhibition of oncogenic miRNAs, and studies now establishing the potential of replacing lost, tumor-suppressive miRNA.
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Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3)Guidi, Mònica 13 January 2009 (has links)
Neurotrophins and their receptors are key molecules in the development of thenervous system. Neurotrophin-3 binds preferentially to its high-affinity receptorNTRK3, which exists in two major isoforms in humans, the full-length kinaseactiveform (150 kDa) and a truncated non-catalytic form (50 kDa). The twovariants show different 3'UTR regions, indicating that they might be differentiallyregulated at the post-transcriptional level. In this work we explore howmicroRNAs take part in the regulation of full-length and truncated NTRK3,demonstrating that the two isoforms are targeted by different sets of microRNAs.We analyze the physiological consequences of the overexpression of some of theregulating microRNAs in human neuroblastoma cells. Finally, we providepreliminary evidence for a possible involvement of miR-124 - a microRNA with noputative target site in either NTRK3 isoform - in the control of the alternativespicing of NTRK3 through the downregulation of the splicing repressor PTBP1. / Las neurotrofinas y sus receptores constituyen una familia de factores crucialespara el desarrollo del sistema nervioso. La neurotrofina 3 ejerce su funciónprincipalmente a través de una unión de gran afinidad al receptor NTRK3, del cualse conocen dos isoformas principales, una larga de 150KDa con actividad de tipotirosina kinasa y una truncada de 50KDa sin dicha actividad. Estas dos isoformasno comparten la misma región 3'UTR, lo que sugiere la existencia de unaregulación postranscripcional diferente. En el presente trabajo se ha exploradocomo los microRNAs intervienen en la regulación de NTRK3, demostrando que lasdos isoformas son reguladas por diferentes miRNAs. Se han analizado lasconsecuencias fisiológicas de la sobrexpresión de dichos microRNAs utilizandocélulas de neuroblastoma. Finalmente, se ha estudiado la posible implicación delmicroRNA miR-124 en el control del splicing alternativo de NTRK3 a través de laregulación de represor de splicing PTBP1.
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