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Arabi, L.* ; Gsponer, J.R.* ; Smida, J. ; Nathrath, M. ; Perrina, V.* ; Jundt, G.* ; Ruiz, C.* ; Quagliata, L.* ; Baumhoer, D.*

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

Genes Cancer 5, 56-63 (2014)
Verlagsversion Volltext PMC
Free by publisher
Creative Commons Lizenzvertrag
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Bim ; Fas ; Mir-106a-363 ; Mir-106b-25 ; Mir-17-92 ; Osteosarcoma
ISSN (print) / ISBN 1947-6019
e-ISSN 1947-6027
Zeitschrift Genes and Cancer
Quellenangaben Band: 5, Heft: 1-2, Seiten: 56-63 Artikelnummer: , Supplement: ,
Verlag Sage
Verlagsort Thousand Oaks, Calif.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CCG Osteosarcoma (PATH-KOS)
Institute of Pathology (PATH)