Evolution of microRNAs expression during human bronchial squamous carcinogenesis

¹ Dept of Intensive Care and Thoracic Oncology; and Research Fellow FNRS (National Fund of Scientific Research)
² Microarrays Unit, DNAVision, Gosselies
³ Dept of Intensive Care and Thoracic Oncology
⁴ Dept of Pathology of Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles (ULB), Brussels
⁵ Dept of Pneumology, CHU Saint-Pierre
⁶ Laboratory of Molecular and Cellular Biology, Faculté Universitaire des Sciences Agronomiques de Gembloux (FUSAGx)

^* To whom correspondence should be addressed. E-mail: celine.mascaux{at}bordet.be.

	Abstract

MicroRNAs, negative posttranscriptional regulators of gene expression, are involved in cancer. Their role in early bronchial carcinogenesis was analysed in 60 biopsies obtained by fluorescence bronchoscopy (6 per stage: normal tissue of non-smokers, normal normofluorescent and hypofluorescent bronchial tissue of smokers, hyperplasia, metaplasia, mild, moderate and severe dysplasia, in situ carcinoma and invasive squamous cell carcinoma (SQCC)).

Seventy microRNAs were found differentially expressed in the course of bronchial carcinogenesis. Among them, some microRNAs show a linear evolution of their expression level like miR-32 and miR-34c, whose expression progressively decrease from normal bronchial tissues of non smokers to SQCC. Others behave differently at successive stages, like miR-142-3p or miR-9, or are only altered from a specific stage, like miR-199a or miR-139. MicroRNAs globally follow a two-steps evolution, first decreasing, in a reverse way of embryogenesis, during the earliest morphological modifications of bronchial epithelium and thereafter increasing at later stages of lung carcinogenesis. Moreover, microRNAs expression is very efficient to predict the histological classification between low and high grade lesions and between in situ and invasive carcinoma.

These 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.