Clinical and functional significance of intracellular and extracellular microRNA-25-3p in Osteosarcoma

Aki Yoshida, Tomohiro Fujiwara, Koji Uotani, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)165-174
Number of pages10
JournalActa medica Okayama
Volume72
Issue number2
Publication statusPublished - 2018

Keywords

  • Circulating microRNA
  • Osteosarcoma
  • Prognosis
  • microRNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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