Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 22, Pages 9184-9189Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1105398108
Keywords
inflammation; cancer; myelofibrosis; noncoding RNA
Categories
Funding
- National Institutes of Health [5R01AI079243-02, 5K99HL102228, 5K08CA133521]
- University of California
- University of California, Los Angeles/Caltech Joint Medical Scientist Training Program
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MicroRNA miR-146a has been implicated as a negative feedback regulator of NF-kappa B activation. Knockout of the miR-146a gene in C57BL/6 mice leads to histologically and immunophenotypically defined myeloid sarcomas and some lymphomas. The sarcomas are transplantable to immunologically compromised hosts, showing that they are true malignancies. The animals also exhibit chronic myeloproliferation in their bone marrow. Spleen and marrow cells show increased transcription of NF-kappa B-regulated genes and tumors have higher nuclear p65. Genetic ablation of NF-kappa B p50 suppresses the myeloproliferation, showing that dysregulation of NF-kappa B is responsible for the myeloproliferative disease.
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