title: Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150.
abstract: Ontogenesis of T cells in the thymus is a complex process whose molecular control is poorly understood. The present study investigated microRNAs involved in human thymocyte differentiation by comparing the microRNA expression profiles of thymocytes at the double-positive, single-positive CD4(+) and single-positive CD8(+) maturation stages. Microarray analysis showed that each thymocyte population displays a distinct microRNA expression profile that reflects their developmental relationships. Moreover, analysis of small-RNA libraries generated from human unsorted and double-positive thymocytes and from mature peripheral CD4(+) and CD8(+) T lymphocytes, together with the microarray data, indicated a trend toward up-regulation of microRNA expression during T-cell maturation after the double-positive stage and revealed a group of microRNAs regulated during normal T-cell development, including miR-150, which is strongly up-regulated as maturation progresses. We showed that miR-150 targets NOTCH3, a member of the Notch receptor family that plays important roles both in T-cell differentiation and leukemogenesis. Forced expression of miR-150 reduces NOTCH3 levels in T-cell lines and has adverse effects on their proliferation and survival. Overall, these findings suggest that control of the Notch pathway through miR-150 may have an important impact on T-cell development and physiology.
authors.affiliation: Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Ghisi
authors.forename: Alberto
authors.initials: A
authors.lastname: Corradin
authors.forename: Katia
authors.initials: K
authors.lastname: Basso
authors.forename: Chiara
authors.initials: C
authors.lastname: Frasson
authors.forename: Valentina
authors.initials: V
authors.lastname: Serafin
authors.forename: Subhamoy
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Lara
authors.initials: L
authors.lastname: Mussolin
authors.forename: Katia
authors.initials: K
authors.lastname: Ruggero
authors.forename: Laura
authors.initials: L
authors.lastname: Bonanno
authors.forename: Alessandro
authors.initials: A
authors.lastname: Guffanti
authors.forename: Gianluca
authors.initials: G
authors.lastname: De Bellis
authors.forename: Gino
authors.initials: G
authors.lastname: Gerosa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stellin
authors.forename: Donna M
authors.initials: DM
authors.lastname: D'Agostino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.forename: Alberto
authors.initials: A
authors.lastname: Amadori
authors.forename: Paola
authors.initials: P
authors.lastname: Zanovello
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D002675:Child, Preschool; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger; D000071656:Receptor, Notch3; D051880:Receptors, Notch; C533097:MIR150, human; C499374:NOTCH3 protein, human