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

doi:10.1165/rcmb.2009-0060oc

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

130 Citations (Scopus)

Abstract

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.

Original language	English
Journal	American Journal of Respiratory Cell and Molecular Biology
Volume	42
Issue number	3
Pages (from-to)	312-9
Number of pages	8
ISSN	1044-1549
DOIs	https://doi.org/10.1165/rcmb.2009-0060oc
Publication status	Published - 1 Mar 2010
Externally published	Yes

Keywords

Aged
Biomarkers, Tumor/genetics
Cell Line, Tumor
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Mesothelioma/diagnosis
MicroRNAs/genetics
Middle Aged
Prognosis
Survival Analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1165/rcmb.2009-0060oc

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@article{7fdf072bb22a4ceca184fd817e4da81f,

title = "MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications",

abstract = "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.",

keywords = "Aged, Biomarkers, Tumor/genetics, Cell Line, Tumor, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Mesothelioma/diagnosis, MicroRNAs/genetics, Middle Aged, Prognosis, Survival Analysis",

author = "Sara Busacca and Serena Germano and {De Cecco}, Loris and Maurizio Rinaldi and Federico Comoglio and Francesco Favero and Bruno Murer and Luciano Mutti and Marco Pierotti and Giovanni Gaudino",

year = "2010",

month = mar,

day = "1",

doi = "10.1165/rcmb.2009-0060oc",

language = "English",

volume = "42",

pages = "312--9",

journal = "American Journal of Respiratory Cell and Molecular Biology",

issn = "1044-1549",

publisher = "American Thoracic Society",

number = "3",

}

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 -

MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications

Abstract

Keywords

UN SDGs

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