Modulation of microRNA expression in human T-cell development: Targeting of NOTCH3 by miR-150

Margherita Ghisi, Alberto Corradin, Katia Basso, Chiara Frasson, Valentina Serafin, Subhamoy Mukherjee, Lara Mussolin, Katia Ruggero, Laura Bonanno, Alessandro Guffanti, Gianluca De Bellis, Gino Gerosa, Giovanni Stellin, Donna M. D'Agostino, Giuseppe Basso, Vincenzo Bronte, Stefano Indraccolo, Alberto Amadori, Paola Zanovello

Research output: Contribution to journalArticlepeer-review

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 doublepositive, single-positive CD4+ and singlepositive 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 microRNAexpression 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.

Original languageEnglish
Pages (from-to)7053-7062
Number of pages10
JournalBlood
Volume117
Issue number26
DOIs
Publication statusPublished - Jun 30 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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