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PMID: 18327259 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes.

Nature immunology ·Vol. 9 ·No. 4 ·2008-04-00 ·Pages 405-14

Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K

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.

MeSH Terms
Animals Autoimmune Diseases/genetics,pathology Cell Death/genetics,immunology Cell Proliferation Cells, Cultured Gene Amplification Gene Expression Regulation, Neoplastic/immunology Humans Jurkat Cells Lymphocyte Activation/genetics,immunology Lymphocytes/immunology,metabolism Lymphoma/genetics,immunology Lymphoproliferative Disorders/genetics,immunology,pathology Mice Mice, Inbred C57BL Mice, Transgenic MicroRNAs/biosynthesis,genetics,physiology
Chemicals
MIRN17 microRNA, human MicroRNAs
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Xiao Changchun
Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Srinivasan Lakshmi
Calado Dinis Pedro
Patterson Heide Christine
Zhang Baochun
Wang Jing
Henderson Joel M
Kutok Jeffrey L
Rajewsky Klaus
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni1575
Published
2008-04-00
Epub
2008-00-09
Pages
405-14
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2533767
Subset
IM
Grants
NIAID NIH HHS · R01 AI064345-03 · United States
NIAID NIH HHS · R01 AI064345-02 · United States
NIAID NIH HHS · R01 AI064345 · United States
NIAID NIH HHS · R01 AI064345-01 · United States
NIAID NIH HHS · AI064345 · United States
Corrections
CommentIn
PMID: 18490933
External Links
PubMed source DOI: 10.1038/ni1575 PMC Full Text View journal details
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