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Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma – reasons and consequences

Osteosarcomas (OS) are aggressive bone tumors characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Although several genes and pathways commonly altered in malignant tumors have also been identified in OS, the molecular pathogenesis and driving ge...

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Autores principales: Arabi, Leila, Gsponer, Joël R, Smida, Jan, Nathrath, Michaela, Perrina, Valeria, Jundt, Gernot, Ruiz, Christian, Quagliata, Luca, Baumhoer, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063253/
https://www.ncbi.nlm.nih.gov/pubmed/24955218
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author Arabi, Leila
Gsponer, Joël R
Smida, Jan
Nathrath, Michaela
Perrina, Valeria
Jundt, Gernot
Ruiz, Christian
Quagliata, Luca
Baumhoer, Daniel
author_facet Arabi, Leila
Gsponer, Joël R
Smida, Jan
Nathrath, Michaela
Perrina, Valeria
Jundt, Gernot
Ruiz, Christian
Quagliata, Luca
Baumhoer, Daniel
author_sort Arabi, Leila
collection PubMed
description Osteosarcomas (OS) are aggressive bone tumors characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Although several genes and pathways commonly altered in malignant tumors have also been identified in OS, the molecular pathogenesis and driving genetic events eventually leading to tumor development are still poorly understood. The microRNA (miRNA) cluster 17-92 and its two paraloga 106a-363 and 106b-25 are known to have diverse oncogenic properties and have been shown to be constantly upregulated in several established OS cell lines. In this study we analyzed a series of 75 well characterized pretherapeutic OS samples for their expression of cluster-related miRNAs and correlated our findings with clinico-pathological parameters including prognosis, metastases and response to neoadjuvant therapy. Interestingly, higher expression levels of specific miRNAs were significantly associated with an adverse outcome of patients and were also higher in patients with systemic spread. We could furthermore show a direct correlation between the expression of cluster activators (MYC, E2F1-3), inhibitors (TP53), individual miRNAs, and pro-apoptotic targets (FAS, BIM). Our findings therefore underline a critical role of the miR-17-92 cluster and its two paraloga in OS biology with pathogenetic and prognostic impact.
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spelling pubmed-40632532014-06-20 Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma – reasons and consequences Arabi, Leila Gsponer, Joël R Smida, Jan Nathrath, Michaela Perrina, Valeria Jundt, Gernot Ruiz, Christian Quagliata, Luca Baumhoer, Daniel Genes Cancer Research Paper Osteosarcomas (OS) are aggressive bone tumors characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Although several genes and pathways commonly altered in malignant tumors have also been identified in OS, the molecular pathogenesis and driving genetic events eventually leading to tumor development are still poorly understood. The microRNA (miRNA) cluster 17-92 and its two paraloga 106a-363 and 106b-25 are known to have diverse oncogenic properties and have been shown to be constantly upregulated in several established OS cell lines. In this study we analyzed a series of 75 well characterized pretherapeutic OS samples for their expression of cluster-related miRNAs and correlated our findings with clinico-pathological parameters including prognosis, metastases and response to neoadjuvant therapy. Interestingly, higher expression levels of specific miRNAs were significantly associated with an adverse outcome of patients and were also higher in patients with systemic spread. We could furthermore show a direct correlation between the expression of cluster activators (MYC, E2F1-3), inhibitors (TP53), individual miRNAs, and pro-apoptotic targets (FAS, BIM). Our findings therefore underline a critical role of the miR-17-92 cluster and its two paraloga in OS biology with pathogenetic and prognostic impact. Impact Journals LLC 2014-01 /pmc/articles/PMC4063253/ /pubmed/24955218 Text en Copyright: © 2014 Arabi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Arabi, Leila
Gsponer, Joël R
Smida, Jan
Nathrath, Michaela
Perrina, Valeria
Jundt, Gernot
Ruiz, Christian
Quagliata, Luca
Baumhoer, Daniel
Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma – reasons and consequences
title Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma – reasons and consequences
title_full Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma – reasons and consequences
title_fullStr Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma – reasons and consequences
title_full_unstemmed Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma – reasons and consequences
title_short Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma – reasons and consequences
title_sort upregulation of the mir-17-92 cluster and its two paraloga in osteosarcoma – reasons and consequences
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063253/
https://www.ncbi.nlm.nih.gov/pubmed/24955218
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