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Author
Yoshida, Aki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Fujiwara, Tomohiro Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Uotani, Koji Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Morita, Takuya Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kiyono, Masahiro Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yokoo, Suguru Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hasei, Joe Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nakata, Eiji Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kunisada, Toshiyuki Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ozaki, Toshifumi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Abstract
Although there is considerable evidence indicating that the dysregulation of microRNAs (miRNAs) in malignant tumors plays a role in tumor development, the overall function of miRNAs and their clinicopathological significance are not well understood. In this retrospective analysis of 45 biopsy specimens from osteosarcoma (OS) patients, we investigated the functional and clinical significance of miR-25-3p in OS, which we previously identified as a highly expressed miRNA in OS patients’ serum. We observed that miR-25-3p dysregulation in human OS tissues was negatively correlated with the clinical prognosis, whereas the expression level of its target gene, Dickkopf WNT Signaling Pathway Inhibitor 3 (DKK3), was positively correlated with the clinical prognosis. Endogenous miR-25-3p upregulation promoted tumor growth, invasion, and drug resistance, which was consistent with DKK3 silencing in OS cells. In addition, secretory miR-25-3p was embedded in tumor-derived exosomes, where it promoted capillary formation and the invasion of vascular endothelial cells. Overall, our results show that miR-25-3p has intracellular and extracellular oncogenic functions as well as clinicopathological relevance in OS, indicating its potential as a novel diagnostic and therapeutic tool for the clinical management of this disease.
Keywords
microRNA
circulating microRNA
osteosarcoma
prognosis
Amo Type
Original Article
Published Date
2018-04
Publication Title
Acta Medica Okayama
Volume
volume72
Issue
issue2
Publisher
Okayama University Medical School
Start Page
165
End Page
174
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
Copyright Holders
CopyrightⒸ 2018 by Okayama University Medical School
File Version
publisher
Refereed
True
PubMed ID