MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications

Sara Busacca, Serena Germano, Loris De Cecco, Maurizio Rinaldi, Federico Comoglio, Francesco Favero, Bruno Murer, Luciano Mutti, Marco Pierotti, Giovanni Gaudino

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs (miRNAs) post-transcriptionally regulate the expression of target genes,andmaybehaveasoncogenesortumorsuppressors. Human malignant mesothelioma is an asbestos-related cancer, with poor prognosis and low median survival. Here we report, for the first time, a cross-evaluation of miRNA expression in mesothelioma (MPP-89, REN) and human mesothelial cells (HMC-telomerase reverse transcriptase). Microarray profiling, confirmed by real-time quantitative RT-PCR, revealed a differential expression of miRNAs between mesothelioma and mesothelial cells. In addition, a computational analysis combining miRNA and gene expression profiles allowed the accurate prediction of genes potentially targeted by dysregulated miRNAs. Several predicted genes belong to terms of Gene Ontology (GO) that are associated with the development and progression of mesothelioma. This suggests that miRNAsmaybe key players in mesothelioma oncogenesis. We further investigated miRNA expression on a panel of 24 mesothelioma specimens, representative of the three histotypes (epithelioid, biphasic, and sarcomatoid), by quantitative RT-PCR. The expression of miR-17-5p, miR-21, miR-29a, miR-30c, miR-30e-5p, miR-106a, and miR-143 was significantly associated with the histopathological subtypes. Notably, the reduced expression of two miRNAs(miR-17-5pandmiR-30c) correlated with better survival of patients with sarcomatoid subtype. Our preliminary analysis points at miRNAs as potential diagnostic and prognostic markers of mesothelioma, and suggests novel tools for the therapy of this malignancy.

Original languageEnglish
Pages (from-to)312-319
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume42
Issue number3
DOIs
Publication statusPublished - Mar 1 2010

Keywords

  • Human malignant mesothelioma
  • Microarray
  • MicroRNAs
  • Real-time quantitative RT-PCR
  • Survival

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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