miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells

Zaidoun Salah, Rand Arafeh, Vadim Maximov, Marco Galasso, Saleh Khawaled, Samah Abou-Sharieha, Stefano Volinia, Kevin B. Jones, Carlo M. Croce, Rami I. Aqeilan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents and young adults. The essential mechanisms underlying osteosarcomagenesis and progression continue to be obscure. MicroRNAs (miRNAs) have far-reaching effects on the cellular biology of development and cancer. We recently reported that unique miRNA signatures associate with the pathogenesis and progression of OS. Of particular interest, we found that higher expression of miR-27a is associated with clinical metastatic disease. We report here that overexpression of miR-27a/miR-27a*, a microRNA pair derived from a single precursor, promotes pulmonary OS metastases formation. By contrast, sequestering miR-27a/miR-27a* by sponge technology suppressed OS cells invasion and metastases formation. miR- 27a/miR-27a* directly repressed CBFA2T3 expression among other target genes. We demonstrated that CBFA2T3 is downregulated in majority of OS samples and its over expression significantly attenuated OS metastatic process mediated by miR-27a/miR- 27a* underscoring CBFA2T3 functions as a tumor suppressor in OS. These findings establish that miR-27a/miR-27a* pair plays a significant role in OS metastasis and proposes it as a potential diagnostic and therapeutic target in managing OS metastases.

Original languageAmerican English
Pages (from-to)4920-4935
Number of pages16
JournalOncotarget
Volume6
Issue number7
DOIs
StatePublished - 2015

Keywords

  • CBFA2T3
  • Metastasis
  • MiR-27a
  • Osteosarcoma
  • Star miRNA

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