miR‑494.3p expression in synovial sarcoma: Role of CXCR4 as a potential target gene

Laura Pazzaglia, Serena Pollino, Mattia Vitale, Elisa Bientinesi, Stefania Benini, Cristina Ferrari, Emanuela Palmerini, Marco Gambarotti, Piero Picci, Maria Serena Benassi

Research output: Contribution to journalArticle

Abstract

Synovial sarcoma (SS) is a rare tumour, with dismal survival when metastasis occurs. SS contains a characteristic translocation (X;18)(p11;q11) and the fusion genes appear to be mutually exclusive and concordant in primary and metastatic tumours. Novel prognostic and predictive factors are required. The C‑X‑C motif chemokine ligand 12 (CXCL12)/C‑X‑C chemokine receptor 4 (CXCR4) axis is involved in tumour development and metastatic spread in many types of cancer and previous data have demonstrated a pivotal role of CXCR4 in SS cell migration and invasion. Bioinformatics and biological data indicated CXCR4 is a possible candidate target of miR‑494.3p, known to be involved in tumour progression. In this study, we analysed the expression of miR‑494.3p and its potential target, CXCR4, in a series of SS specimens. A significantly lower miR‑494.3p expression was found in the tumour compared to normal tissue associated with higher levels of CXCR4 both at the gene and protein level. The role of CXCR4 as a potential target of miR‑494.3p was assessed in two SS cell lines (SW982 and SYO‑I). Transfection with miR‑494.3p expression plasmid led to a marked decrease in CXCR4 gene and protein expression, concomitant with a transitory decrease in cell proliferation and migration. The SYO‑I cells also responded with an increased apoptotic fraction. The data of this study also demonstrate that the downregulation of miR‑494.3p in SS surgical specimens, concomitant with an increased expression of its potential target, CXCR4, was more evident in the metastatic subset. In vitro experiments confirmed that miR‑494.3p functioned as a tumour suppressor through the involvement of CXCR4 and ongoing studies are directed to better clarify its role in SS therapeutic strategies.

Original languageEnglish
Pages (from-to)361-369
Number of pages9
JournalInternational Journal of Oncology
Volume54
Issue number1
DOIs
Publication statusE-pub ahead of print - Nov 6 2018

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Keywords

  • synovial sarcoma
  • microRNA‑494.3p
  • C‑X‑C chemokine receptor 4
  • biomarker
  • cell migration

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