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Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):E1695-704. doi: 10.1073/pnas.1201516109. Epub 2012 Jun 8.

Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma.

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Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.


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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