title: HMGA1-pseudogene expression is induced in human pituitary tumors.
abstract: Numerous studies have established that High Mobility Group A (HMGA) proteins play a pivotal role on the onset of human pituitary tumors. They are overexpressed in pituitary tumors, and, consistently, transgenic mice overexpressing either the Hmga1 or the Hmga2 gene develop pituitary tumors. In contrast with HMGA2, HMGA1 overexpression is not related to any rearrangement or amplification of the HMGA1 locus in these tumors. We have recently identified 2 HMGA1 pseudogenes, HMGA1P6 and HMGA1P7, acting as competitive endogenous RNA decoys for HMGA1 and other cancer related genes. Here, we show that HMGA1 pseudogene expression significantly correlates with HMGA1 mRNA levels in growth hormone and nonfunctioning pituitary adenomas likely inhibiting the repression of HMGA1 through microRNAs action. According to our functional studies, these HMGA1 pseudogenes enhance the proliferation and migration of the mouse pituitary tumor cell line, at least in part, through their upregulation. Our results point out that the overexpression of HMGA1P6 and HMGA1P7 could contribute to increase HMGA1 levels in human pituitary tumors, and then to pituitary tumorigenesis.
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche; Scuola di Medicina e Chirurgia di Napoli; Università degli Studi di Napoli "Federico II" , Naples , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Esposito
authors.forename: Marco
authors.initials: M
authors.lastname: De Martino
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Angelo
authors.forename: Paula
authors.initials: P
authors.lastname: Mussnich
authors.forename: Gerald
authors.initials: G
authors.lastname: Raverot
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Jaffrain-Rea
authors.forename: Filippo
authors.initials: F
authors.lastname: Fraggetta
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trouillas
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D024003:HMGA Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011544:Pseudogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D024003:HMGA Proteins; D012333:RNA, Messenger
keywords: HMGA1; HMGA1P6; HMGA1P7; ceRNA; miRNA