TY - JOUR
T1 - MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications
AU - Busacca, Sara
AU - Germano, Serena
AU - De Cecco, Loris
AU - Rinaldi, Maurizio
AU - Comoglio, Federico
AU - Favero, Francesco
AU - Murer, Bruno
AU - Mutti, Luciano
AU - Pierotti, Marco
AU - Gaudino, Giovanni
PY - 2010/3/1
Y1 - 2010/3/1
N2 - MicroRNAs (miRNAs) post-transcriptionally regulate the expression of target genes, and may behave as oncogenes or tumor suppressors. 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 miRNAs may be 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-17-5p and miR-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.
AB - MicroRNAs (miRNAs) post-transcriptionally regulate the expression of target genes, and may behave as oncogenes or tumor suppressors. 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 miRNAs may be 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-17-5p and miR-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.
KW - Aged
KW - Biomarkers, Tumor/genetics
KW - Cell Line, Tumor
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Male
KW - Mesothelioma/diagnosis
KW - MicroRNAs/genetics
KW - Middle Aged
KW - Prognosis
KW - Survival Analysis
U2 - 10.1165/rcmb.2009-0060oc
DO - 10.1165/rcmb.2009-0060oc
M3 - Journal article
C2 - 19502386
SN - 1044-1549
VL - 42
SP - 312
EP - 319
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 3
ER -
