title: Altered microRNA expression profile in human pituitary GH adenomas: down-regulation of miRNA targeting HMGA1, HMGA2, and E2F1.
abstract: BACKGROUND
  MicroRNA (miRNA) are an important class of regulators of gene expression. Altered miRNA expression has been constantly found in human neoplasias and plays an important role in the process of carcinogenesis.
  
  
  OBJECTIVE
  The aim of this study was to identify specific miRNA whose expression is altered in GH-secreting pituitary adenomas.
  
  
  METHODS
  Using a miRNACHIP microarray, we have analyzed the miRNA expression profile of human GH adenomas vs. normal pituitary gland.
  
  
  RESULTS
  We report the identification of a set of miRNA, including miR-34b, miR-326, miR-432, miR-548c-3p, miR-570, and miR-603, drastically and constantly down-regulated in GH adenomas. We demonstrate that these miRNA target genes such as high-mobility group A1 (HMGA1), HMGA2, and E2F1, whose overexpression and/or activation plays a critical role in pituitary tumorigenesis. We also show that the enforced expression of the down-regulated miRNA has a negative role on the growth regulation of pituitary adenoma cells. Finally, an inverse correlation is found between the expression of these miRNA and HMGA1 and HMGA2 protein levels in GH adenomas.
  
  
  CONCLUSIONS
  Our study identifies a specific subset of miRNA, whose down-regulation might contribute to pituitary tumorigenesis.
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche (CNR) c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita` degli Studi di Napoli, Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Angelo
authors.forename: Dario
authors.initials: D
authors.lastname: Palmieri
authors.forename: Paula
authors.initials: P
authors.lastname: Mussnich
authors.forename: Magali
authors.initials: M
authors.lastname: Roche
authors.forename: Anne
authors.initials: A
authors.lastname: Wierinckx
authors.forename: Gerald
authors.initials: G
authors.lastname: Raverot
authors.forename: Monica
authors.initials: M
authors.lastname: Fedele
authors.forename: Carlo Maria
authors.initials: CM
authors.lastname: Croce
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trouillas
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics* / Q000473:pathology; D057809:HEK293 Cells; D025741:HMGA1a Protein / Q000235:genetics*; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D046228:Microarray Analysis; D010911:Pituitary Neoplasms / Q000235:genetics; D015175:Prolactinoma / Q000235:genetics
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D025743:HMGA2 Protein; D035683:MicroRNAs; D025741:HMGA1a Protein