Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 26, Pages E1695-E1704Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1201516109
Keywords
oncogene; oncomiR addiction; nanotechnology
Categories
Funding
- Gilliam Fellowship (Howard Hughes Medical Institute)
- James S. McDonnell Foundation
- National Institutes of Health
- Yale Cancer Center
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MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of miR-155 in lymphoid tissues results in disseminated lymphoma characterized by a clonal, transplantable pre-B-cell population of neoplastic lymphocytes. Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these addicted pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.
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