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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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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. |
format | Online Article Text |
id | pubmed-4063253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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