title: Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes.
abstract: The genomic region encoding the miR-17-92 microRNA (miRNA) cluster is often amplified in lymphoma and other cancers, and cancer cells carrying this amplification have higher expression of miRNA in this cluster. Retroviral expression of miR-17-92 accelerates c-Myc-induced lymphoma development, but precisely how higher expression of miR-17-92 promotes lymphomagenesis remains unclear. Here we generated mice with higher expression of miR-17-92 in lymphocytes. These mice developed lymphoproliferative disease and autoimmunity and died prematurely. Lymphocytes from these mice showed more proliferation and less activation-induced cell death. The miR-17-92 miRNA suppressed expression of the tumor suppressor PTEN and the proapoptotic protein Bim. This mechanism probably contributed to the lymphoproliferative disease and autoimmunity of miR-17-92-transgenic mice and contributes to lymphoma development in patients with amplifications of the miR-17-92 coding region.
authors.affiliation: Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Changchun
authors.initials: C
authors.lastname: Xiao
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Srinivasan
authors.forename: Dinis Pedro
authors.initials: DP
authors.lastname: Calado
authors.forename: Heide Christine
authors.initials: HC
authors.lastname: Patterson
authors.forename: Baochun
authors.initials: B
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Joel M
authors.initials: JM
authors.lastname: Henderson
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Kutok
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000473:pathology; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology
chemical_list: C524941:MIRN17 microRNA, human; D035683:MicroRNAs