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Evolution of microRNA expression during human bronchial squamous carcinogenesis

¹ Dept of Intensive Care and Thoracic Oncology, and ³ Dept of Pathology, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, ⁴ Dept of Pneumology, CHU Saint-Pierre, Brussels, ² Microarrays Unit, DNAVision, and, Gosselies, and ⁵ Laboratory of Molecular and Cellular Biology, Faculté Universitaire des Sciences Agronomiques de Gembloux, Gembloux, Belgium, ⁶ Both authors contributed equally to this article.

CORRESPONDENCE: C. Mascaux, Institut Jules Bordet, Rue Héger-Bordet 1, B-1000 Brussels, Belgium. Fax: 32 25343756. E-mail: celine.mascaux{at}bordet.be

Keywords: Carcinogenesis, lung, lung cancer, microRNAs, premalignant

Received: June 4, 2008
Accepted October 1, 2008

MicroRNAs, negative post-transcriptional regulators of gene expression, are involved in cancer.

Their role in early bronchial carcinogenesis was analysed in 60 biopsies obtained by fluorescence bronchoscopy (six per stage: normal tissue of nonsmokers, normal normofluorescent and hypofluorescent bronchial tissue of smokers, hyperplasia, metaplasia, mild, moderate and severe dysplasia, in situ carcinoma and invasive squamous cell carcinoma (SQCC)).

In total, 69 microRNAs were found to be differentially expressed in the course of bronchial carcinogenesis. Among them, some microRNAs showed a linear evolution of their expression level, such as miR-32 and miR-34c, whose expression progressively decreased from normal bronchial tissues of nonsmokers to SQCC. Others behaved differently at successive stages, such as miR-142-3p or miR-9, or are only altered from a specific stage, such as miR-199a or miR-139. MicroRNAs globally followed a two-step evolution, first decreasing (a reverse of their increase during embryogenesis) during the earliest morphological modifications of bronchial epithelium, and thereafter increasing at later stages of lung carcinogenesis. Moreover, microRNA expression was very efficient for the prediction of the histological classification between low- and high-grade lesions and between in situ and invasive carcinoma.

The present data show, for the first time, that microRNAs are involved in bronchial carcinogenesis from the very early steps of this process and, thus, could provide tools for early detection of lung cancer.