Changes in
microRNAs (
miRNAs) expression in many types of
cancer suggest that they may be involved in crucial steps during
tumor progression. Indeed,
miRNAs deregulation has been described in pituitary
tumorigenesis, but few studies have described their role in
pituitary tumor progression toward aggressiveness and
malignancy. To assess the role of
miRNAs within the hierarchical cascade of events in
prolactin (PRL)
tumors during progression, we used an integrative genomic approach to associate clinical-pathological features, global
miRNA expression, and transcriptomic profiles of the same human
tumors. We describe the specific down-regulation of one principal
miRNA, miR-183, in the 8 aggressive (A, grade 2b) compared to the 18 non-aggressive (NA, grades 1a, 2a) PRL
tumors. We demonstrate that it acts as an anti-proliferative gene by directly targeting KIAA0101, which is involved in cell cycle activation and inhibition of p53-p21-mediated cell cycle arrest. Moreover, we show that miR-183 and KIAA0101 expression significantly correlate with the main markers of
pituitary tumors aggressiveness, Ki-67 and p53. These results confirm the activation of proliferation in aggressive and malignant PRL
tumors compared to non-aggressive ones. Importantly, these data also demonstrate the ability of such an integrative genomic strategy, applied in the same human
tumors, to identify the molecular mechanisms responsible for tumoral progression even from a small cohort of patients.