title: Deregulation of miR-183 and KIAA0101 in Aggressive and Malignant Pituitary Tumors.
abstract: 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.
authors: Centre de Recherche en Cancérologie de Lyon, INSERM U1052/CNRS UMR 5286 Centre Léon Bérard , Lyon , France ; Université Lyon 1, Université de Lyon , Lyon , France ; ViroScan3D , Trévoux , France.
authors: Magali
authors: M
authors: Roche
authors: Centre de Recherche en Cancérologie de Lyon, INSERM U1052/CNRS UMR 5286 Centre Léon Bérard , Lyon , France ; Université Lyon 1, Université de Lyon , Lyon , France ; ProfileXpert, SFR-Est, CNRS UMR-S3453, INSERM US7 , Lyon , France.
authors: Anne
authors: A
authors: Wierinckx
authors: Université Lyon 1, Université de Lyon , Lyon , France ; ProfileXpert, SFR-Est, CNRS UMR-S3453, INSERM US7 , Lyon , France.
authors: Séverine
authors: S
authors: Croze
authors: ProfileXpert, SFR-Est, CNRS UMR-S3453, INSERM US7 , Lyon , France.
authors: Catherine
authors: C
authors: Rey
authors: Université Lyon 1, Université de Lyon , Lyon , France ; ViroScan3D , Trévoux , France ; ProfileXpert, SFR-Est, CNRS UMR-S3453, INSERM US7 , Lyon , France ; UMR CNRS 5557 UCBL USC INRA 1193 ENVL, Dynamique Microbienne et Transmission Virale , Lyon , France.
authors: Catherine
authors: C
authors: Legras-Lachuer
authors: Centre de Recherche en Cancérologie de Lyon, INSERM U1052/CNRS UMR 5286 Centre Léon Bérard , Lyon , France.
authors: Anne-Pierre
authors: AP
authors: Morel
authors: Instituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli "Federico II" , Naples , Italy ; Instituto Nacional de Câncer (INCA) , Rio de Janeiro , Brazil.
authors: Alfredo
authors: A
authors: Fusco
authors: Université Lyon 1, Université de Lyon , Lyon , France ; UMR 5292, Centre de Neurosciences de Lyon, CNRS, INSERM S1028 , Lyon , France ; Fédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon , Lyon , France.
authors: Gérald
authors: G
authors: Raverot
authors: Université Lyon 1, Université de Lyon , Lyon , France ; UMR 5292, Centre de Neurosciences de Lyon, CNRS, INSERM S1028 , Lyon , France ; Centre de Pathologie Est, Groupement Hospitalier Est, Hospice Civils de Lyon , Bron , France.
authors: Jacqueline
authors: J
authors: Trouillas
authors: Centre de Recherche en Cancérologie de Lyon, INSERM U1052/CNRS UMR 5286 Centre Léon Bérard , Lyon , France ; Université Lyon 1, Université de Lyon , Lyon , France ; ProfileXpert, SFR-Est, CNRS UMR-S3453, INSERM US7 , Lyon , France.
authors: Joel
authors: J
authors: Lachuer
keywords: PRL tumor; aggressiveness; integrative genomics; malignancy; miRNA; pituitary tumor